tbuckley/cabot-search huggingface dataset:
Efficacy and tolerability of sorafenib in elderly patients with advanced hepatocellular carcinoma.
Authors: H. Wong, C. C. Yau, T. Yao, V. Tang, P. Chan, J. Chiu, S. Fan, R. Poon
Journal: Journal of Clinical Oncology (2010)

e14522 Background: With the aging population, malignancies, including hepatocellular carcinoma (HCC) in the elderly represent a significant health burden. The perception that older cancer patients may be at higher risk than younger patients of toxic effects from cancer therapy but may obtain less clinical benefit from it is mainly due to known toxic effects of cytotoxic chemotherapy. It is not known how older patients respond to targeted therapy. We aim to evaluate and compare the efficacy and tolerability of single agent sorafenib in treating elderly and younger patients with advanced HCC. Methods: We retrospectively analysed consecutive advanced HCC patients treated with sorafenib between November 2006 and December, 2009 in our centre. The patients were categorized into older (age ≥ 70 years) and younger (age < 70 years) groups. The demographic data, sorafenib-related toxicities and survival outcome were compared between these two age groups. Progression-free survival (PFS) and overall survival (OS) were analysed by the Kaplan-Meier method. Results: A total of 177 patients, 25 and 152 in the elderly (median age 74.6 years) and younger group (median age 55.9 years) respectively, were analysed. Median PFS was similar in the older and younger group (13.7 weeks vs. 13.0 weeks, p = 0.61, log-rank test), as was the median OS (20.71 weeks vs. 19.4 weeks, p = 0.64). Grade 3 or 4 adverse events were observed in 40.0% of the older and 52.0% of the younger patients respectively (p = 0.27, χ2 test). Malaise (12.0% vs. 2.6%, p = 0.06) and neutropenia (8.0% vs. 0.7%, p = 0.05, Fisher's exact test) were more common in the elderly group than in the younger group. The proportion of patients requiring drug interruption or dose reduction was similar among the older patients and the younger patients (44.0% vs. 40.8%, p = 0.76, χ2 test), while 12.0% of the older group and 9.9% of the younger group (p = 0.72) permanently stopped sorafenib due to toxicities. Conclusions: The efficacy and tolerability of sorafenib is similar in treating elderly and younger patients with advanced HCC. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Bayer Bayer
Value of adjuvant radiation therapy in breast cancer patients with one to three positive lymph nodes undergoing a modified radical mastectomy and systemic therapy
Authors: S. Dawood, A. M. Gonzalez-Angulo, W. Woodward, F. Meric-Bernstam, K. Hunt, A. Buzdar, G. Hortobagyi, T. Buchholz
Journal: Journal of Clinical Oncology (2009)

507 Background: Whether adjuvant radiation therapy should be utilized for patients (pts) with early stage breast cancer with up to 3 positive axillary lymph nodes treated with mastectomy and systemic therapy is controversial. This retrospective study was performed to determine if adjuvant radiation therapy had an impact on survival for this cohort of pts. Methods: 4240 pts with T1–2N0–1 breast cancers, diagnosed between 1980–2007, who underwent either mastectomy without adjuvant radiation therapy or segmental mastectomy with adjuvant radiation therapy were identified. All pts received systemic treatment. Women with &gt;3 positive axillary lymph nodes were excluded. Overall (OS) and distant disease free survival (DDFS) were estimated using the Kaplan-Meir product method. Cox proportional hazards were used to determine associations between OS/DDFS and type of surgery after controlling for pt and disease characteristics. Results: 1336 (18.8%) had T1N0 disease, 1114 (26.27%) had T2N0 disease, 989 (23.33%) had T1N1 disease and 801 (18.89%) had T2N1 disease. Median follow-up was 54 months.5- year DDFS among women who underwent mastectomy and segmental mastectomy was 81% (95% 78%-83%) and 86% (95% CI 84%-87%), respectively (p &lt; 0.0001). In the Cox analysis, pts who had mastectomy without radiation had a significantly increased risk of distant recurrence (HR= 1.39, 95% CI 1.14–1.70, p= 0.0013) than pts treated with segmental mastectomy and radiation. When looking at subgroups, no significant difference in DDFS was observed between the two groups in pts with lymph node negative disease. However, for pts with 1–3 positive lymph nodes, pts treated with mastectomy without radiation had significantly increased risk of distant recurrence compared to pts treated with segmental mastectomy with radiation (HR=1.614, 95% CI 1.198–2.177, p= 0.002). This difference was most pronounce in the subset of patients with T2N1 disease (HR= 1.794, 95% CI 1.220–2.637, p=0.003). Similar trends were observed for OS. Conclusions: This study provides provocative evidence for benefit of radiation therapy among pts with 1–3 positive axillary lymph nodes who are treated with surgery and systemic therapy. No significant financial relationships to disclose.
Final results of a randomized, double-blind, active-controlled trial of darbepoetin alfa administered once every 3 weeks (Q3W) for the treatment of anemia in patients receiving multicycle chemotherapy
Authors: J.-L. Canon, J. Vansteenkiste, G. Bodoky, M. V. Mateos, L. Bastit, I. Ferreira, G. Rossi
Journal: Journal of Clinical Oncology (2005)

LBA8284 Background: Chemotherapy-induced anemia (CIA) often results in debilitating fatigue that can be alleviated with erythropoietic agents, epoetin alfa and darbepoetin alfa (DA). The ability to administer DA on a Q3W schedule to synchronize with the majority of chemotherapy regimens is of particular interest to clinicians and patients. The objective of this study is to evaluate and compare the efficacy and safety of Q3W with once-weekly (QW) DA using a non-inferiority approach. This is the largest study to date to examine efficacy of DA in the treatment of CIA using a fixed dose with extended dosing. Methods: This is a randomized, double-blind, active-controlled, phase 3 trial in 160 centers across Europe. Eligibility include age ≥18 years, anemia (hemoglobin [Hb] <11g/dL), and nonmyeloid malignancy with ≥12 weeks (wks) of planned chemotherapy. Patients (pts) were randomized 1:1 to either 2.25mcg/kg QW or 500mcg Q3W DA, stratified by tumor type, screening Hb (<10 or ≥10g/dL) and region. Pts in the Q3W treatment arm received QW placebo to maintain the double-blind nature and to avoid bias in treatment decisions. Pts were treated up to 16 wks. The primary endpoint is the incidence of transfusions from wk 5 to end of treatment period (EOTP). Other clinically meaningful endpoints include change in Hb, change in FACT-Fatigue scores and achievement of Hb ≥11g/dL from wk 5 to EOTP in the absence of transfusions. Analyses will be based on data from pts who received ≥1 dose of study medication. Kaplan-Meier estimates, adjusted for stratification factors, for each treatment arm will be compared using log-rank test. For the primary endpoint, a two-sided 95% confidence interval (CI) for the difference (Q3W-QW) in transfusion rates will be calculated. If the upper limit of the CI is ≤12.5% (based on previous studies of DA 2.25mcg/kg), then non-inferiority of the Q3W regimen to the QW regimen will be concluded. Two-sided 95% CI will also be calculated for the difference in mean Hb change of the treatment groups adjusting for stratification and baseline factors. Results: Final transfusion incidence rates on 705 pts will be presented. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Amgen Amgen, AstraZeneca, Aventis, Bristol-Myers Squibb, Eli Lilly Amgen Amgen, Eli Lilly
Statistical Explanations for a Community-Based Study of Once-Weekly Epoetin Alfa Therapy in Patients Receiving Chemotherapy
Authors: Janice L. Gabrilove, Brenda Sarokhan, Pierre Cremieux
Journal: Journal of Clinical Oncology (2002)

Article Tools SPECIAL DEPARTMENTS Article Tools OPTIONS & TOOLS Export Citation Track Citation Add To Favorites Rights & Permissions COMPANION ARTICLES No companion articles ARTICLE CITATION DOI: 10.1200/JCO.2002.20.11.2757 Journal of Clinical Oncology - published online before print September 21, 2016 PMID: 12039942 Statistical Explanations for a Community-Based Study of Once-Weekly Epoetin Alfa Therapy in Patients Receiving Chemotherapy Janice L. GabrilovexJanice L. GabriloveSearch for articles by this author , Brenda SarokhanxBrenda SarokhanSearch for articles by this author , Pierre CremieuxxPierre CremieuxSearch for articles by this author Show More Mount Sinai Medical Center, New York, NYOrtho Biotech Products, LP, Raritan, NJAnalysis Group/Economics, Cambridge, MA https://doi.org/10.1200/JCO.2002.20.11.2757 First Page Full Text PDF Figures and Tables © 2002 by American Society of Clinical Oncology
Abstract 15444: Removal of Circulating Beta-1 Autoantibodies in Patients With Dilated Cardiomyopathy Can Improve Survival on Transplantation Lists and Spare Some Patients From Transplantation or Mechanical Circulatory Support
Authors: Michael Dandel, Angela Englert, Gerd Wallukat, Christoph Knosalla, Roland Hetzer
Journal: Circulation (2013)

Background:  With prolongation of waiting times for heart transplantatation (HTx) new therapies are needed to improve survival on HTx lists and to provide treatment alternatives for older persons who become less eligible for HTx. Patients with dilated cardiomyopathy (DCM) were often tested positive for β 1 -autoantibodies (β 1 -AABs) and their removal by immunoadsorption (IA) can improve cardiac function, but the usefulness of IA for end-stage heart failure therapy, especially in older patients with LVEF    METHODS:  Cardiac function and survival without HTx or ventricular assist device (VAD) support were evaluated in HTx candidates with dilated cardiomyopathy (DCM) and LVEF ≤ 25% who underwent unspecific IA (unselective antibody removal) in 7/1995 - 2/207 (follow-up 5.3 – 11.7 yrs). Before and after IA patients were tested for serum β 1 -autoantibodies (β 1 -AABs).   RESULTS:  During the 1 st  year after IA the 82 β 1 -AAB positive patients who fulfilled all inclusion criteria showed improvement (p   5 years was reached by 49 patients (59.8%). IA removed the β 1 -AABs in 81 patients (98.8%) and of these, 53 (65.4%) also fulfilled the “responder” criteria (LVEF increase with > 15%). The 53 responders showed an average 45% increase of LVEF (from 20 ± 4% to 29 ± 6%). The Benefits from IA were similar for patients below the age of 55 (n = 49; age 42 ± 8 yrs) and beyond this age (n = 33; age 59 ± 3 yrs). Redetection of β 1 -AABs (in 15 pts before and in 5 pts after the 5 th  post-IA year) coincided with cardiac worsening.  The 21 β 1 -AAB negative patients showed lower HTx/VAD-free survival in comparison with the β 1 -AAB positive patients (p    CONCLUSION:  Unspecific IA which effectively removes circulating β 1 -AABs is an efficient therapeutic option for β 1 -AAB positive DCM patients with LVEF ≤ 25% regardless their age. It can improve heart function allowing long-term stability which can delay HTx listing for many years and even spare patients from HTx or VAD insertion, benefits of particular importance for older patients who are at higher risk for HTx.
Mutations in <i>TUBB8</i> and Human Oocyte Meiotic Arrest
Authors: Ruizhi Feng, Qing Sang, Yanping Kuang, Xiaoxi Sun, Zheng Yan, Shaozhen Zhang, Juanzi Shi, Guoling Tian, Anna Luchniak, Yusuke Fukuda, Bin Li, Min Yu, Junling Chen, Yao Xu, Luo Guo, Ronggui Qu, Xueqian Wang, Zhaogui Sun, Miao Liu, Huijuan Shi, Hongyan Wang, Yi Feng, Ruijin Shao, Renjie Chai, Qiaoli Li, Qinghe Xing, Rui Zhang, Eva Nogales, Li Jin, Lin He, Mohan L. Gupta, Nicholas J. Cowan, Lei Wang
Journal: New England Journal of Medicine (2016)

Background Human reproduction depends on the fusion of a mature oocyte with a sperm cell to form a fertilized egg. The genetic events that lead to the arrest of human oocyte maturation are unknown. Methods We sequenced the exomes of five members of a four-generation family, three of whom had infertility due to oocyte meiosis I arrest. We performed Sanger sequencing of a candidate gene, TUBB8, in DNA samples from these members, additional family members, and members of 23 other affected families. The expression of TUBB8 and all other β-tubulin isotypes was assessed in human oocytes, early embryos, sperm cells, and several somatic tissues by means of a quantitative reverse-transcriptase-polymerase-chain-reaction assay. We evaluated the effect of the TUBB8 mutations on the assembly of the heterodimer consisting of one α-tubulin polypeptide and one β-tubulin polypeptide (α/β-tubulin heterodimer) in vitro, on microtubule architecture in HeLa cells, on microtubule dynamics in yeast cells, and on spindle assembly in mouse and human oocytes. Results We identified seven mutations in the primate-specific gene TUBB8 that were responsible for oocyte meiosis I arrest in 7 of the 24 families. TUBB8 expression is unique to oocytes and the early embryo, in which this gene accounts for almost all the expressed β-tubulin. The mutations affect chaperone-dependent folding and assembly of the α/β-tubulin heterodimer, disrupt microtubule behavior on expression in cultured cells, alter microtubule dynamics in vivo, and cause catastrophic spindle-assembly defects and maturation arrest on expression in mouse and human oocytes. Conclusions TUBB8 mutations have dominant-negative effects that disrupt microtubule behavior and oocyte meiotic spindle assembly and maturation, causing female infertility. (Funded by the National Basic Research Program of China and others.).
To Dement or Not to Dement, That Is the Question
Authors: Bryan J. Traynor, Yevgeniya A. Abramzon
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
Vandetanib with pemetrexed in patients with previously treated non-small cell lung cancer (NSCLC): An open-label, multicenter phase I study
Authors: R. De Boer, J. Vansteenkiste, Y. Humblet, J. Wolf, L. Nogova, K. Ruffert, R. Smith, A. Godwood, T. Milenkova
Journal: Journal of Clinical Oncology (2007)

7654 Background: Vandetanib (ZD6474) is a once-daily oral anticancer drug that selectively inhibits VEGF-dependent tumor angiogenesis and EGFR- and RET-dependent tumor cell proliferation and survival. Methods: Eligible patients had locally advanced or metastatic NSCLC (stage IIIB/IV) after failure of 1 st -line chemotherapy. An initial cohort of 10 patients received once- daily oral vandetanib (100 mg) with pemetrexed (500 mg/m 2 i.v. infusion every 21 days). If &lt;2 patients experienced a vandetanib- related dose-limiting toxicity (DLT), an additional cohort received vandetanib 300 mg + pemetrexed. The planned duration of treatment was =6 weeks. The primary objective of the study was to establish the safety and tolerability of vandetanib + pemetrexed. Secondary objectives included an assessment of pharmacokinetic (PK) interaction and preliminary assessment of efficacy (RECIST). Results: Twenty- one patients (14 male, 7 female; mean age 60 years, range 44–77) received vandetanib 100 mg + pemetrexed (n=10) or vandetanib 300 mg + pemetrexed (n=11). One DLT was reported in each cohort: QTc prolongation (&gt;100 ms from baseline, but absolute QTc &lt;500 ms) in a male patient who had electrolyte imbalance and short baseline QTc interval of 318 ms (100 mg cohort); and interstitial lung disease, which resolved after steroid therapy, in a Caucasian female patient with bronchoalveolar carcinoma and a long smoking history (300 mg cohort). The most common adverse events (AEs) were rash, anorexia, fatigue and diarrhea (all n=10; 48%). The most frequent CTC grade 3/4 AEs were increased gamma-glutamyltransferase (n=4), anorexia (n=3) and dyspnea (n=3), which are generally consistent with previous experience with vandetanib and pemetrexed as monotherapies. There was no apparent PK interaction between vandetanib and pemetrexed. In 18 patients evaluable for efficacy, there was one confirmed partial response (female; 100 mg cohort) and 13 stable disease =6 weeks. Conclusions: In patients with advanced NSCLC, vandetanib + pemetrexed was generally well tolerated, with no apparent PK interaction. A Phase III trial of vandetanib 100 mg + pemetrexed in 2nd-line NSCLC has begun. No significant financial relationships to disclose.
Results from the seminal vesicle sparing prostatectomy trial.
Authors: Scott Michael Gilbert, Rodney Dunn, Jeffrey Scott Montgomery, David Miller, Ted A. Skolarus, Alon Weizer, David Peter Wood, Brent K. Hollenbeck
Journal: Journal of Clinical Oncology (2014)

55 Background: Prostate cancer accounts for greater than 200,000 cases each year. Although cancer control is generally favorable with treatment, side effects are common. Among men treated with surgery, nerve-sparing prostatectomy is associated with lower rates of incontinence and erectile dysfunction. Seminal vesicle sparing (SVS) may further limit damage to the neurovascular tissue surrounding the prostate. Although some surgeons practice SVS, evidence supporting its use is lacking. We implemented a randomized control trial to determine if SVS is associated with better functional outcomes compared to non-SVS prostatectomy. Methods: 140 men with early-stage (T1c/T2N0M0, Gleason score &lt;= 7) prostate cancer and adequate erectile function (IIEF &gt;= 21) were enrolled in the Seminal Vesicle Sparing Prostatectomy Trial (NCT01825642) and randomized to either SVS or non-SVS prostatectomy between 2006 and 2011. The Expanded Prostate Cancer Index Composite (EPIC) was used to assess quality of life outcomes following surgery. Results: 71 and 69 men were enrolled in the SVS and non-SVS arms, respectively. The predominant surgical approach was robotic assisted prostatectomy (&gt;97% in both arms). Men in the SVS arm were slightly younger (56 vs 58 years, p = 0.02); however, there were no significant differences in other clinical or demographic factors. There were no cases of seminal vesicle invasion. PSA recurrence was noted in 3 patients (1 in SVS group and 2 in non-SVS group). At 12 months postoperatively, sexual (76 vs 75) and urinary incontinence (92 vs 94) scores were similar among SVS and non-SVS patients (both p &gt; 0.2). Conclusions: Recovery of urinary and sexual function was common among men undergoing SVS or non-SVS prostatectomy. SVS did not negatively impact cancer control, but was not associated with enhanced recovery of sexual or urinary function, perhaps due to the high level of recovery of the control arm. Clinical trial information: NCT01825642. [Table: see text]
Abstract 9797: Nur77 Inhibits Pulmonary Artery Smooth Muscle Cell Proliferation Though Targeting the STAT3/Pim-1/NFAT Axis
Authors: Yan Liu, Jian Zhang, Bing Yi, Ming Chen, Jia Qi, Jian Xin Sun
Journal: Circulation (2013)

The orphan nuclear receptor 4A (NR4A) family plays critical roles in the regulation of cell proliferation, differentiation, and survival in cardiovascular system. However, the molecular mechanism underlying the regulation of NR4A receptor expression and its functional significance in pulmonary artery smooth muscle cell (PASMC) proliferation remain unclear. Here we investigated whether NR4A family regulates PASMC proliferation, and if so, to determine the mechanism involved. By using quantitative real-time PCR (qRT-PCR), we showed that orphan nuclear receptor Nur77 was the most abundant member of NR4A family expressed in rat PASMCs, as compared to other two members, NOR-1 and Nurr1. In rat PASMCs, the expression of Nur77 was robustly induced in response to several pathologic stimuli implicated in pulmonary artery hypertension (PAH), such as hypoxia, 5-hydroxytryptamine (5-HT), platelet derived growth factor (PDGF), and endothelin-1. Importantly, the protein levels of Nur77 are significantly increased in the lungs of monocrotaline (MCT) induced PAH rats. Furthermore, we demonstrated that 5-HT, a potent mitogen for PASMC, markedly up-regulated the Nur77 expression, through mitogen activated protein kinases/extracellular signal-regulated kinase 1/2 (MAPK/Erk1/2) pathway in rat PASMCs. Overexpression of Nur77 markedly inhibited 5-HT induced cell proliferation, and the expression of Cyclin D1 and proliferating cell nuclear antigen (PCNA) in rat PASMCs. Moreover, knockdown of Nur77 augments the 5-HT induced PASMC proliferation. Mechanistically, we demonstrated that Nur77 specifically interacts with STAT3, thus inhibiting its phosphorylation and the expression of its target genes, such as Pim-1, NFATc2, and survivin in PASMCs, which are critical for the PASMC proliferation and the development of PAH. These results indicate that Nur77 is a novel negative regulator for PASMC proliferation through inhibiting the STAT3/Pim-1/NFAT axis. Modulation of Nur77 activity may potentially represent a novel therapeutic strategy for the treatment of PAH.
Atypical Teratoid/Rhabdoid Tumors Are Comprised of Three Epigenetic Subgroups with Distinct Enhancer Landscapes
Authors: Pascal D. Johann, Serap Erkek, Marc Zapatka, Kornelius Kerl, Ivo Buchhalter, Volker Hovestadt, David T.W. Jones, Dominik Sturm, Carl Hermann, Maia Segura Wang, Andrey Korshunov, Marina Rhyzova, Susanne Gröbner, Sebastian Brabetz, Lukas Chavez, Susanne Bens, Stefan Gröschel, Fabian Kratochwil, Andrea Wittmann, Laura Sieber, Christina Geörg, Stefan Wolf, Katja Beck, Florian Oyen, David Capper, Peter van Sluis, Richard Volckmann, Jan Koster, Rogier Versteeg, Andreas von Deimling, Till Milde, Olaf Witt, Andreas E. Kulozik, Martin Ebinger, Tarek Shalaby, Michael Grotzer, David Sumerauer, Josef Zamecnik, Jaume Mora, Nada Jabado, Michael D. Taylor, Annie Huang, Eleonora Aronica, Anna Bertoni, Bernhard Radlwimmer, Torsten Pietsch, Ulrich Schüller, Reinhard Schneppenheim, Paul A. Northcott, Jan O. Korbel, Reiner Siebert, Michael C. Frühwald, Peter Lichter, Roland Eils, Amar Gajjar, Martin Hasselblatt, Stefan M. Pfister, Marcel Kool
Journal: Cancer Cell (2016)