tbuckley/cabot-search huggingface dataset:
Phase I study of vorinostat plus docetaxel in patients with solid tumor malignancies
Authors: B. J. Schneider, D. Bradley, D. C. Smith, M. Egorin, G. Kalemkerian, R. Dunn, S. Daignault, M. Hussain
Journal: Journal of Clinical Oncology (2009)

2528 Background: Vorinostat is an inhibitor of histone deacetylase 6, which results in the acetylation of tubulin and the stabilization of microtubules. Since taxanes bind to stabilized microtubules, the administration of vorinostat followed by docetaxel, we hypothesized, should result in synergistic cytotoxicity. A phase I trial was conducted to determine the dose level of vorinostat plus docetaxel that would result in dose-limiting toxicity (DLT) in ≤ 30% of patients (pts). Methods: Eligible pts had castration-resistant prostate cancer (CRPC) or relapsed urothelial or non-small-cell lung cancer (NSCLC) after ≥1 prior chemotherapy regimen not containing docetaxel, a performance status of 0–2 and adequate organ function. Vorinostat was given orally for 14 days beginning on day 1 of a 21-day cycle. Docetaxel was given intravenously over 1 hour on day 4. The time-to-event continuous reassessment method guided dose escalation. Dose levels (DL) -1, 0, 1 and 2 corresponded to vorinostat 100, 100, 200 and 200 mg plus docetaxel 50, 60, 60, and 75 mg/m 2 , respectively. Blood was collected on days 1 and 4 of cycle 1 to measure drug levels by HPLC. Results: 12 pts were enrolled: median age 65 yrs (49–74); gender 9M:3F; 4 CRPC, 5 urothelial, 3 NSCLC. The median number of cycles was 2. 2 pts were treated at DL -1, 4 pts at DL 0, 5 pts at DL 1 and 1 pt at DL 2. 5 DLTs occurred in 5 pts: grade 4 neutropenic fever/sepsis (n = 2), anaphylactic reaction (n = 1), myocardial infarction (n = 1) and GI bleed (n = 1). Other toxicities included grade 4 neutropenia (n = 2), pulmonary embolus (n = 1) and GI bleed (n = 1). The estimated probability of DLT for DL -1 was .32 (90% posterior probability interval [PI], .11 to .53) for DL 0, .38 (90% PI, .16 to .58) and for DL 1, .43 (90% PI, .23 to .64). The trial was stopped due to excessive toxicity. No responses were noted. Conclusions: Combination vorinostat plus docetaxel was poorly tolerated with excessive DLTs requiring study termination. PK analysis will be presented. Supported in part by a grant from Merck &amp; Co., Inc. [Table: see text]
The problem of mixed cellularity lymphoma.
Authors: M D Goodyear
Journal: Journal of Clinical Oncology (1986)

Article Tools Article Tools OPTIONS & TOOLS Export Citation Track Citation Add To Favorites Rights & Permissions COMPANION ARTICLES No companion articles ARTICLE CITATION DOI: 10.1200/JCO.1986.4.2.263 Journal of Clinical Oncology - published online before print September 22, 2016 PMID: 3944609 The problem of mixed cellularity lymphoma. M D GoodyearxM D GoodyearSearch for articles by this author https://doi.org/10.1200/JCO.1986.4.2.263 PDF "The problem of mixed cellularity lymphoma.." Journal of Clinical Oncology, 4(2), pp. 263–264© 1986 by American Society of Clinical Oncology
Simultaneous and independent control of a brain-computer interface and contralateral limb movement
Authors: Ivana Milovanovic, Robert Robinson, Eberhard E. Fetz, Chet T. Moritz
Journal: Brain-Computer Interfaces (2015)

Toward expanding the population of potential BCI users to the many individuals with lateralized cortical stroke, here we examined whether the cortical hemisphere controlling ongoing movements of the contralateral limb can simultaneously generate signals to control a BCI. A monkey was trained to perform a simultaneous BCI and manual control task designed to test whether one hemisphere could effectively differentiate its output and provide independent control of two tasks. Pairs of well-isolated single units were used to control a BCI cursor in one dimension, while isometric wrist torque of the contralateral forelimb controlled the cursor in a second dimension. The monkey could independently modulate cortical units and contralateral wrist torque regardless of the strength of directional tuning of the units controlling the BCI. When the presented targets required explicit decoupling of unit activity and wrist torque, directionally tuned units exhibited significantly less efficient cursor trajectories compared to when unit activity and wrist torque could remain correlated. The results indicate that neural activity from a single hemisphere can be effectively decoupled to simultaneously control a BCI and ongoing limb movement, suggesting that BCIs may be a viable future treatment for individuals with lateralized cortical stroke.
Influence of sub-specialty surgical care on outcomes for pediatric emergency general surgery patients in a low-middle income country
Authors: Adil A. Shah, Amarah Shakoor, Cheryl K. Zogg, Tolulope Oyetunji, Awais Ashfaq, Erin M. Garvey, Asad Latif, Robert Riviello, Faisal G. Qureshi, Arif Mateen, Adil H. Haider, Hasnain Zafar
Journal: International Journal of Surgery (2016)
Kinase-sensing system to identify the oncogenic phospho-fingerprint of breast cancer.
Authors: Miki Mori, Zhongzhong Chen, Aaron Boudreau, Laura van't Veer, Jean-Philippe Coppe
Journal: Journal of Clinical Oncology (2013)

23 Background: Kinases and their substrates harness myriad critical molecular pathways. A new highly valuable assay would be one detecting the true active state of phospho-signaling networks. To address this technological and knowledge gap, we developed a semi-high throughput sensing system that monitors the catalytic activity of kinases using peptides as phosphorylation targets/probes. We used this assay to evaluate the presence of dysfunctional kinases in biological extracts and identify oncogenic phospho-signatures prevalent in breast cancer. Methods: We developed a human kinase protein and peptide repertoire computationally curated from thousands of publications. Out of the 2,702 validated peptide targets and 6,173 kinase-substrate nodes we compiled, we chose a subset of 151 biological peptides predicted to specifically report on tyrosine / serine / threonine kinases, including EGFR, ERK, AKT, SRC, ABL. Along with 91 control peptides, we tested a total of 242 peptides in a luminescence ATP-consumption assay for their ability to report on the kinases’ activity. The assay was further validated using an isogenic culture model of basal like breast cancer (HMT-3522 S1 and T4-2), and cell lines harboring various oncogenic alterations (MDA-MB-231, MCF7, T47D, AU565, ZR75.1, SKBR3). Results: The differential phosphorylation activity of recombinant kinase enzymes was successfully detected in time course, dilution and inhibitor experiments. The increased presence of (hyper-) activated SRC, EGFR, AKT or ABL kinases observed by western blots in subsets of breast cancer cells, was selectively, repeatedly and specifically detected using the peptide-based kinase assay. Significantly altered peptide-phosphorylation patterns were successfully integrated into signatures using gene expression microarray-like analysis, revealing the breast cancer-associated map of phosphorylation circuits. Conclusions: This assay is suitable to comprehensively capture the activity of kinase signaling networks. We will now use this functional proteomic assay to identify the active, oncogenic kinome of breast cancer, with the objective to improve clinical guidance and individualize breast cancer patients’ therapy.
Distinct Contribution of Adult-Born Hippocampal Granule Cells to Context Encoding
Authors: Nathan B. Danielson, Patrick Kaifosh, Jeffrey D. Zaremba, Matthew Lovett-Barron, Joseph Tsai, Christine A. Denny, Elizabeth M. Balough, Alexander R. Goldberg, Liam J. Drew, René Hen, Attila Losonczy, Mazen A. Kheirbek
Journal: Neuron (2016)
<i>De Novo</i> DQ Donor-Specific Antibodies Are Associated with Chronic Lung Allograft Dysfunction after Lung Transplantation
Authors: Jussi M. Tikkanen, Lianne G. Singer, S. Joseph Kim, Yanhong Li, Matthew Binnie, Cecilia Chaparro, Chung-Wai Chow, Tereza Martinu, Sassan Azad, Shaf Keshavjee, Kathryn Tinckam
Journal: American Journal of Respiratory and Critical Care Medicine (2016)

Rationale: Despite increasing evidence about the role of donor-specific human leukocyte antigen (HLA) antibodies in transplant outcomes, the incidence and impact of de novo donor-specific antibodies (dnDSA) after lung transplantation remains unclear.Objectives: To describe the incidence, characteristics, and impact of dnDSA after lung transplantation.Methods: We investigated a single-center cohort of 340 lung transplant recipients undergoing transplant during 2008 to 2011. All patients underwent HLA-antibody testing quarterly pretransplant and at regular intervals over the first 24 months after transplant. The patients received modified immunosuppression depending on their pretransplant sensitization status. Risk factors for dnDSA development, as well as the associations of dnDSA with patient survival and chronic lung allograft dysfunction (CLAD), were determined using multivariable analysis.Measurements and Main Results: The cumulative incidence of dnDSA was 47% at a median of 86 days (range, 44–185 d) after lung transplantation. Seventy-six percent of recipients with dnDSA had DQ-DSA. Male sex and the use of ex vivo lung perfusion were associated with an increased risk of dnDSA, whereas increased HLA-DQB1 matching was protective. DQ-dnDSA preceded or coincided with the diagnosis of CLAD in all cases. Developing dnDSA (vs. no dnDSA) was associated with a twofold increased risk of CLAD (hazard ratio, 2.04; 95% confidence interval, 1.13–3.69). This association appeared to be driven by the development of DQ-dnDSA.Conclusions: dnDSA are common after lung transplantation, with the majority being DQ DSA. DQ-dnDSA are associated with an increased risk of CLAD. Strategies to prevent or treat DQ-dnDSA may improve outcomes for lung transplant recipients.
A Difficult Case: Case report
Authors: R J Davenport, I R Starkey, C V Ruckley, M S Dennis, P A G Sandercock, C P Warlow
Journal: BMJ (1995)

A Dificult CaseHow should a patient presenting with unstable angina and a recent stroke be managed?The occurrence of stroke in a patient with unstable angina is a common problem, particularly when preparing patients for bypass surgery.R J Davenport and colleagues present a difficult case of a man with this condition.Several experts not concerned with the case give their views on how he might be treated.
Soliciting BCI user experience feedback from people with severe speech and physical impairments
Authors: Betts Peters, Aimee Mooney, Barry Oken, Melanie Fried-Oken
Journal: Brain-Computer Interfaces (2016)

Brain–computer interface (BCI) researchers have shown increasing interest in soliciting user experience (UX) feedback, but the severe speech and physical impairments (SSPI) of potential users create barriers to effective implementation with existing feedback instruments. This article describes augmentative and alternative communication (AAC)-based techniques for obtaining feedback from this population, and presents results from administration of a modified questionnaire to 12 individuals with SSPI after trials with a BCI spelling system. The proposed techniques facilitated successful questionnaire completion and provision of narrative feedback for all participants. Questionnaire administration required less than 5 minutes and minimal effort from participants. Results indicated that individual users may have very different reactions to the same system, and that ratings of workload and comfort provide important information not available through objective performance measures. People with SSPI are critical stakeholders in the future development of BCI, and appropriate adaptation of feedback questionnaires and administration techniques allows them to participate in shaping this assistive technology.
Cancer Patient Survival Among Ethnic Groups in the United States
Authors: John L. Young, Lynn Gloeckler Ries, Earl S. Pollack
Journal: JNCI Journal of the National Cancer Institute (1984)

Data from the Surveillance, Epidemiology and End Results Program of the National Cancer Institute were used in the evaluation of cancer patient survival experience for 8 racial-ethnic groups in the U.S. population—Anglos, Hispanics, blacks, American Indians, Chinese, Japanese, Filipinos, and Hawaiians. This report contains an actuarial (life table) survival analysis on 402,752 patients with first primary cancer diagnosed in 1973-79 and followed through December 31, 1981. Relative and observed survival rates are shown for each sex separately by primary site. Survival rates for females exceeded those for males for each primary site except for gallbladder and urinary bladder. The primary site having the highest survival rate among each group studied was the thyroid gland with a 5-year relative rate of 91% for all races combined. Rates were uniformly low among each group for cancers of the esophagus, liver, and pancreas. Survival rates for Hispanics were almost identical to those for Anglos; the largest differences were found for bladder (73% for Anglos vs. 64% for Hispanics), Hodgkin's disease (70% for Anglos vs. 61% for Hispanics), and ovary (35% for Anglos vs. 42% for Hispanics). For many primary sites Japanese experienced the highest survival rates and American Indians the lowest. In comparison to Anglos, Japanese had higher survival for cancers of the stomach, colon, prostate gland, and breast. The higher survival for stomach and breast cancers persisted even when controlling for age of patient and stage of disease at diagnosis. Survival rates for blacks were much lower than those for whites for cancers of the corpus uteri and urinary bladder. Survival rates for Chinese and Hawaiians were roughly comparable to those for Anglos, whereas survival rates for Filipinos tended to be similar to those for blacks.
A phase II trial of imatinib mesylate in Merkel cell carcinoma (neuroendocrine carcinoma of the skin): A Southwest Oncology Group Study (S0331)
Authors: W. E. Samlowski, J. Moon, R. J. Tuthill, M. C. Heinrich, N. S. Balzer-Haas, S. A. Merl, R. C. DeConti, J. A. Thompson, L. E. Flaherty, V. K. Sondak
Journal: Journal of Clinical Oncology (2009)

9056 Background: Merkel cell carcinoma (MCC, neuroendocrine carcinoma of the skin) frequently stains strongly for c-KIT (CD-117) expression. We therefore evaluated imatinib mesylate as a treatment for MCC. Methods: Eligibility included patients with measurable metastatic or unresectable MCC with CD117 expression by immunostaining. A Zubrod performance status of 0–2, adequate hematologic, renal, and hepatic function was also required. Imatinib 400 mg daily was administered orally in 28-day cycles. Results: A total of 25 patients were accrued to this trial from 13 institutions, with 6 accrued through Intergroup participation by the Eastern Cooperative Oncology Group. Two patients were ineligible (one was found not to express CD117 on central pathology review, and one lacked measurable disease). These 23 patients were included in the analysis. Imatinib was well tolerated with Grade 1 or 2 nausea, diarrhea, and hematologic toxicity as the most frequent side effects. There were no complete responses (0%) and 1 confirmed partial response (4%) in the 23 evaluable patients (4% objective response rate, CI 0 -22%). In addition, stable disease was observed in 3 patients (9, 4 and 3 months). Median progression-free survival was 1 month (95% CI: 1–2 months). Estimated 6 month PFS was 4%. Median overall survival was 5 months (95% CI 2–8 months). The estimated one-year overall survival was 17% (95% CI: 0% - 33%). There were three on-study deaths. All were attributed to tumor progression. One patient achieved a partial response and another had prolonged disease stabilization while receiving treatment. DNA sequencing of c-KIT was performed on tumor tissue from on a non- responding patient and the one patient with long-term stable disease (9 months). Neither demonstrated an activating mutation in c-KIT. Unfortunately, the patient with partial response withdrew consent for the study and DNA sequencing could not be performed. Conclusions: The majority of patients progressed rapidly within 1–2 cycles of treatment. The observed progression-free survival and overall survival were not adequate to conclude that this agent was active in advanced MCC. The planned second stage of patient accrual was not opened. No significant financial relationships to disclose.
Abstract MP084: Childhood and Adult Environmental Tobacco Smoke and Risk of Incident Type 2 Diabetes Among Never-smoking French Women
Authors: Martin Lajous, Laura Tondeur, Blandine de Lauzon-Guillain, Guy Fagherazzi, Marie-Christine Boutron-Ruault, Francoise Clavel-Chapelon
Journal: Circulation (2012)

Background There is consistent evidence of a direct relation between active smoking and type 2 diabetes. However, prior studies on passive smoking (or secondhand smoke) and type 2 diabetes have often been limited by insufficiently detailed information on both childhood and adult environmental tobacco smoke exposure. Methods and Results We evaluated childhood and adult environmental tobacco exposure (ETS) in relation to incident type 2 diabetes in a prospective cohort study among 37,343 never-smoker women from the E3N-EPIC cohort, who were free of diabetes, cancer or cardiovascular disease at baseline in 1992. Self-reported childhood ETS was defined as having at least one parent who smoked (59 % of women). Adult ETS exposure was defined as the sum of self-reported hours of exposure to tobacco from a smoking spouse (or domestic close contact) and exposure to ETS outside the home, recorded at baseline. Between 1992 and 2007, 795 cases of incident diabetes were identified and validated using a drug reimbursement dataset and a specifically designed supplementary questionnaire. Adjusting for family history of diabetes, education and body silhouette at age 18 women with at least one smoking parent had an 18 % higher rate of diabetes compared to women with nonsmoking parents [HR=1.18 (95%CI 1.02-1.86)]. After additional adjustment for physical activity, BMI, parental smoking, treated hypertension and hypercholesterolemia, menopausal status and menopausal hormone use the multivariate HRs (95%CI) for adult ETS exposure relative to no exposure were 1.08 (0.92, 1.27) for &lt; 1 hours/day, 1.06 (0.77, 1.46) for 1 to 1.9 hours/day, 1.34 (1.00, 1.82) for 2 to 3.9 hours/day and 1.44 (1.11, 1.86) for ≥ 4 hours/ day with p for trend 0.003. Conclusion Childhood and adult ETS exposure may be associated to a higher rate of type 2 diabetes. These results further emphasize the health risks of past and current tobacco smoke exposure.
Positive Effect on Multiple Sclerosis With Treatment of Metabolic Syndrome
Authors: Aiden Haghikia, Ralf Gold
Journal: JAMA Neurology (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 Neurology 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 Neurology journal
Quantitative Phosphotyrosine Profiling of Patient-Derived Xenografts Identifies Therapeutic Targets in Pediatric Leukemia
Authors: Sibasish Dolai, Keith C.S. Sia, Alissa K. Robbins, Ling Zhong, Sue L. Heatley, Tiffaney L. Vincent, Falko Hochgräfe, Rosemary Sutton, Raushan T. Kurmasheva, Tamas Revesz, Deborah L. White, Peter J. Houghton, Malcolm A. Smith, David T. Teachey, Roger J. Daly, Mark J. Raftery, Richard B. Lock
Journal: Cancer Research (2016)

Activating mutations in tyrosine kinases (TKs) drive pediatric high-risk acute lymphoblastic leukemia (ALL) and confer resistance to standard chemotherapy. Therefore, there is urgent need to characterize dysregulated TK signaling axes in patients with ALL and identify actionable kinase targets for the development of therapeutic strategies. Here, we present the first study to quantitatively profile TK activity in xenografted patient biopsies of high-risk pediatric ALL. We integrated a quantitative phosphotyrosine profiling method with 'spike-in' stable isotope labeling with amino acids in cell culture (SILAC) and quantified 1394 class I phosphorylation sites in 16 ALL xenografts. Moreover, hierarchical clustering of phosphotyrosine sites could accurately classify these leukemias into either B or T-cell lineages with the high-risk early T-cell precursor (ETP) and Ph-like ALL clustering as a distinct group. Furthermore, we validated this approach by using specific kinase pathway inhibitors to perturb ABL1, FLT3, and JAK TK signaling in four xenografted patient samples. By quantitatively assessing the tyrosine phosphorylation status of activated kinases in xenograft models of ALL, we were able to identify and validate clinically relevant targets. Therefore, this study highlights the application and potential of phosphotyrosine profiling for identifying clinically relevant kinase targets in leukemia.
Disease-Free Survival Of Myelodysplastic Syndrome After Allogeneic Hematopoietic Stem Cell Transplantation Is Not Associated With Disease Status and Donor Sources
Authors: Yue Lu, Tong Wu, Xing-Yu Cao, Yan-Li Zhao, De-Yan Liu, Jia-Rui Zhou, Min Xiong, Jian-Ping Zhang, Rui-Juan Sun, Zhi-Jie Wei, Shu-Quan Ji, Dao-Pei Lu
Journal: Blood (2013)
Impact of Adjuvant Treatment Modalities on Survival Outcomes in Curatively Resected Pancreatic and Periampullary Adenocarcinoma
Authors: N. Turan, M. Benekli, O.U. Unal, I.T. Unek, D. Tastekin, F. Dane, E. Algin, S. Ulger, T. Eren, T.O. Topcu, E. Turkmen, N.A. Babacan, G. Tufan, Z. Urakci, B.B. Ustaalioglu, O.S. Uysal, O.B. Ercelep, B.Y. Taskoylu, A. Aksoy, M. Canhoroz
Journal: Annals of Oncology (2014)
Exhaled Breath Analysis for Monitoring Response to Treatment in Advanced Lung Cancer
Authors: Inbar Nardi-Agmon, Manal Abud-Hawa, Ori Liran, Naomi Gai-Mor, Maya Ilouze, Amir Onn, Jair Bar, Dekel Shlomi, Hossam Haick, Nir Peled
Journal: Journal of Thoracic Oncology (2016)
Role of Transient Elastography (Fibroscan) in Differentiating Severe Acute Hepatitis and Acute on Chronic Liver Failure
Authors: Rinkesh Kumar Bansal, Praveen Sharma, Pankaj Tyagi, Ashish Kumar, Vikas Singla, Naresh Bansal, Anil Arora
Journal: Clinical Gastroenterology and Hepatology (2015)