tbuckley/cabot-search huggingface dataset:
Phase I trial of the novel epothilone sagopilone (ZK-EPO) in combination with cisplatin as first-line therapy in patients with extensive-disease small-cell lung cancer (ED-SCLC)
Authors: T. C. Gauler, D. C. Christoph, F. Gamarra, H. Fuhr, C. Gonschorek, M. Giurescu, N. Frickhofen, R. M. Huber, M. Schuler, W. E. E. Eberhardt
Journal: Journal of Clinical Oncology (2008)

19081 Background: Sagopilone, a novel epothilone, has shown preclinical activity against SCLC cell lines. A completed Phase I trial with sagopilone in various solid tumors has demonstrated single-agent administration to be well tolerated with peripheral neuropathy as the major dose-limiting toxicity (DLT). Early signals of clinical efficacy, including objective responses, have been observed. This study aimed to determine the maximum tolerated dose (MTD) of sagopilone combined with cisplatin (P) as 1st-line treatment in patients (pts) with ED-SCLC. Methods: Pts with chemotherapy-naïve ED-SCLC and measurable disease were included. Treatment consisted of a 3-h infusion of sagopilone followed by a fixed dose of P (75 mg/m2 1-h infusion) d1 q3w. Dose escalation of sagopilone included 12 mg/m2 (1st cohort), 16 mg/m2 (2nd cohort), and 22 mg/m2 (3rd cohort). At each dose level (DL) 6 pts were planned. Dose escalation would be stopped in the event of >1 DLT per cohort. Results: Until 12/2007, 16 pts were treated (12 male, 4 female): 6 pts at 1st DL (12 mg/m2 sagopilone, 75 mg/m2 P), 7 pts at 2nd DL, and 3 pts at 3rd DL. The median age was 60 years (range 43–72). Complete data are currently available for 13 pts. A median of 5 cycles per pt has been administered. So far, MTD has not been reached: no DLTs were observed at DL 1 or 2. One pt experienced DLT at 22 mg/m2 (grade 3 bone pain). The most commonly observed drug-related side effect was peripheral sensory neuropathy (7/13 patients): 1 pt, grade 1; 5 pts, grade 2; 1 pt, grade 3. Other drug-related toxicities (all grades ≥10%) were nausea (54%), vomiting (54%), pain extremities (38%), anemia (31%), fatigue (31%), anorexia (23%), pain other (23%), vertigo (23%), constipation (15%), and headache (15%). Preliminary efficacy analysis showed objective responses in 6/12 (50%) evaluable pts (all partial responses). Conclusions: In ED-SCLC, a combination of 75 mg/m2 P and sagopilone up to a dose of 16 mg/m2 can be safely administered. Final results of the 3rd cohort at 22 mg/m2 will be available at the meeting. The combination of P and sagopilone has shown promising clinical activity in pts with ED-SCLC. Further Phase II evaluation of this combination in ED-SCLC appears to be warranted. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Bayer Schering Pharma AG Bayer Schering AG Bayer Schering AG Bayer Schering AG Bayer Schering Pharma AG Roche Pharma AG
Outcomes for patients with advanced GIST achieving a complete remission (CR) with imatinib (IM): Results from the prospective randomized phase III trial of the French Sarcoma Group
Authors: A. Cioffi, A. Dufresne, A. Italiano, M. Rios, A. Blesius, F. Bertucci, A. Adenis, S. Darnis, A. Le Cesne, J. Y. Blay
Journal: Journal of Clinical Oncology (2008)

10550 Background: IM is the first-line treatment for advanced GIST and must be given continuously until disease progression or intolerance. The pattern of response to IM is heterogeneous. Patient (pt) characteristics and outcome of pts experiencing a CR under IM are unknown. Methods: Since June 2002, 378 pts with advanced GIST have been included in the BFR14 trial. Fifteen pts (4%) achieved a CR during treatment. Their characteristics were compared to those of the entire cohort of pts not randomized in the stopping arms (at 1 and 3 yrs) and to those of pts who underwent a surgery of residual disease after inclusion. The outcome of these pts was compared to the entire population receiving IM continuously and to pts experienced a PR and stable disease according to RECIST criteria. Results: Pts achieving a CR with IM had a significant lower tumor volume (p=0.01) and a low neutrophil count (p=0.06) at inclusion. There were no differences between the 2 groups of pts for all other parameters analyzed. After a median follow-up of 21 months, the progression-free survival (PFS) of these 15 pts (2-yrs PFS = 84.4%) was significantly higher than the whole cohort of pts (p=0.01) and significantly higher than pts exhibiting a PR (2-yrs PFS = 63.3%) or a SD (2-yrs PFS = 27.9%) (p< 0.0001). The 3-yr overall survival (OS) was 85.7%, 80.7% and 48.6% for pts achieving a CR, PR and SD, respectively (p = 0.0054). Among the 7 pts with CR for which a mutational analysis was performed, one pt harbors a kit exon 9 mutation and two a WT GIST. Conclusions: Pts with advanced GIST achieving a CR with IM have a low tumor load at inclusion and have a favorable outcome. Obtention of CR seems not related to a particular genetic alteration of kit/PDGFR. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Novartis Novartis Novartis Novartis
Should single agents be standard therapy for urothelial tract tumors?
Authors: H I Scher
Journal: Journal of Clinical Oncology (1989)

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.1989.7.6.694 Journal of Clinical Oncology - published online before print September 22, 2016 PMID: 2715800 Should single agents be standard therapy for urothelial tract tumors? H I ScherxH I ScherSearch for articles by this author Show More Memorial Sloan-Kettering Cancer Center, New York. https://doi.org/10.1200/JCO.1989.7.6.694 First Page PDF © 1989 by American Society of Clinical Oncology
Abstract 14665: Higher Numbers of Circulating Endothelial Progenitor Cells are Associated with Better Functional Performance in Patients with Peripheral Artery Disease
Authors: Rana Saber, Harris Perlman, Kiang Liu, Huimin Tao, Lihui Zhao, Mary McDermott
Journal: Circulation (2012)

Objectives: Growing evidence suggests that circulating endothelial progenitor cells (EPCs) repair damaged endothelium in patients with cardiovascular disease. Ischemia, induced by walking activity ...
A combination of mitoxantrone, etoposide and prednisone in elderly patients with non-Hodgkin's lymphoma
Authors: L. Salvagno, A. Contu, A. Bianco, L. Endrizzi, G.M. Schintu, N. Olmeo, S.M.L. Aversa, V. Chiarion-Sileni, M. Sorarú, M.V. Fiorentino
Journal: Annals of Oncology (1992)
What is the optimum number of beams and energy for IMRT boost in prostate cancer? A plan comparison study
Authors: H. Kunhiparambath, R. Prabhakar, G. K. Rath, D. N. Sharma, P. Heera, P. K. Julka
Journal: Journal of Clinical Oncology (2009)

e16158 Background: Intensity Modulated Radiotherapy (IMRT) is used in carcinoma prostate to achieve better target coverage with less dose to critical organs thereby permitting dose escalation and eventually better therapeutic ratio. There is scarcity of literature evaluating beam number and energy in prostate cancer treated by IMRT. Aim of our study is to identify the optimal number of beams and energy in the boost treatment of prostate cancer by IMRT. Methods: Ten patients were included in this study. Initially a dose of 45 Gy in 25 fractions was delivered to the prostate, seminal vesicles and the nodes by 3DCRT. A boost dose of 27 Gy in 15 fractions was planned to the prostate and the seminal vesicles by sliding window IMRT. Four different sets of IMRT plans: 5, 7 and 9 field with 6 MV; 7 field with 15 MV were generated. The dose constraints to the critical structures and the target volume were based on standard guidelines. The mean dose, maximum dose, volume receiving the prescribed dose (V100), volume receiving &gt; 107% and &lt;95% of the prescribed dose were analyzed for CTV and planning target volume (PTV). The mean dose, volume receiving 100%, 50% and 30% of the prescribed dose were analyzed for the bladder and the rectum. Similarly, the mean dose and the maximum dose to the right and left femoral heads, monitor units (MU) and the integral dose were analyzed. SPSS V10.0 software was used for statistical analysis. Results: The seven beam plan provide better dose homogeneity to PTV and lesser doses to critical structures like bladder, rectum and femoral heads when 6 MV photon is used. 15 MV photons further improve the dose homogeneity and decrease the dose to critical structures. The Monitoring Units required to deliver the treatment and the Integral dose is significantly reduced by using 15 MV compared to 6 MV. Conclusions: The optimal IMRT plan for boost planning in carcinoma prostate is that uses 7 beams and higher energy. This yields lesser dose to surrounding critical structures with better target conformity. [Table: see text] No significant financial relationships to disclose.
No need for contralateral lung surgery in case of evidence of post-chemotherapy necrosis alone in residual lung masses in patients with disseminated non seminomatous germ cell tumors
Authors: B. Besse, A. Flechon, A. Caty, C. Chevreau, S. Culine, D. Grunenwald, K. Fizazi
Journal: Journal of Clinical Oncology (2005)

4524 Background: Resection of residual lesions after primary chemotherapy and normalization of serum tumor markers is part of the multimodality treatment of advanced non seminomatous germ cell tumors (NSGCT). Multiple resections are currently recommended in case of multiple sites of residual disease. Methods: A multicenter retrospective study of 71 pts with thoracic residual masses after first-line cisplatin-based chemotherapy for disseminated NSGCT. Results: The histologic findings in residual lesions included complete necrosis, teratoma, and viable cancer in 31%, 55%, and 14% of patients, respectively. Discordant histopathologic findings were evidenced between retroperitoneal lymph node and thoracic (lung or mediastinal lymph nodes) residual masses in 31% of cases (n= 52). For example, 3 of the 15 pts with necrosis (20%) alone in RPLND had either teratoma or viable cancer in their lung metastases. In contrast, only 2 of 39 patients (5%) who had a bilateral pulmonary resection had discordant histological findings between the 2 lungs. Of 20 patients with necrosis alone in residual masses in the first lung, 19 (95%) also had necrosis alone in residual masses in their contralateral lung. Only one patient had necrosis alone in the first lung and some mature teratoma in the contralateral lung. Conclusions: These results support published data on discordant histopathologic findings between retroperitoneal and thoracic residual masses. Most importantly, they show that the pathologic concordance rate between the 2 lungs is high. Therefore, we recommend avoiding contralateral lung surgery when only necrosis is found in the first lung after primary chemotherapy for NSGCT. No significant financial relationships to disclose.
Phase I/II Trial of IDEC-Y2B8 Radioimmunotherapy for Treatment of Relapsed or Refractory CD20<sup>+</sup>B-Cell Non-Hodgkin's Lymphoma
Authors: Thomas E. Witzig, Christine A. White, Gregory A. Wiseman, Leo I. Gordon, Christos Emmanouilides, Andrew Raubitschek, Nalini Janakiraman, John Gutheil, Russell J. Schilder, Stewart Spies, Daniel H.S. Silverman, Elizabeth Parker, Antonio J. Grillo-López
Journal: Journal of Clinical Oncology (1999)

PURPOSE: Yttrium-90 ibritumomab tiuxetan (IDEC-Y2B8) is a murine immunoglobulin G1 kappa monoclonal antibody that covalently binds MX-DTPA (tiuxetan), which chelates the radioisotope yttrium-90. The antibody targets CD20, a B-lymphocyte antigen. A multicenter phase I/II trial was conducted to compare two doses of unlabeled rituximab given before radiolabeled antibody, to determine the maximum-tolerated single dose of IDEC-Y2B8 that could be administered without stem-cell support, and to evaluate safety and efficacy. PATIENTS AND METHODS: Eligible patients had relapsed or refractory (two prior regimens or anthracycline if low-grade disease) CD20 + B-cell low-grade, intermediate-grade, or mantle-cell non-Hodgkin's lymphoma (NHL). There was no limit on bulky disease, and 59% had at least one mass ≥ 5 cm. RESULTS: The maximum-tolerated dose was 0.4 mCi/kg IDEC-Y2B8 (0.3 mCi/kg for patients with baseline platelet counts 100 to 149,000/μL). The overall response rate for the intent-to-treat population (n = 51) was 67% (26% complete response [CR]; 41% partial response [PR]); for low-grade disease (n = 34), 82% (26% CR; 56% PR); for intermediate-grade disease (n = 14), 43%; and for mantle-cell disease (n = 3), 0%. Responses occurred in patients with bulky disease (≥ 7 cm; 41%) and splenomegaly (50%). Kaplan-Meier estimate of time to disease progression in responders and duration of response is 12.9+ months and 11.7+ months, respectively. Adverse events were primarily hematologic and correlated with baseline extent of marrow involvement with NHL and baseline platelet count. One patient (2%) developed an anti-antibody response (human antichimeric antibody/human antimouse antibody). CONCLUSION: These phase I/II data demonstrate that IDEC-Y2B8 radioimmunotherapy is a safe and effective alternative for outpatient therapy of patients with relapsed or refractory NHL. A phase III study is ongoing.
The use of chloroplast DNA to resolve plant phylogenies: noncoding versus rbcL sequences.
Authors: L Gielly, P Taberlet
Journal: Molecular Biology and Evolution (1994)

Direct sequencing of polymerase chain reaction products is now an expanding area of plant systematics and evolution. Within angiosperms the rbcL gene has been widely sequenced and used for inferring plant phylogenies at higher taxonomic levels. Unfortunately rbcL does not usually contain enough information to resolve relationships between closely related genera, such as Hordeum, Triticum, and Aegilops. One solution to this problem could be to analyze noncoding regions of chloroplast DNA, which are supposed to evolve more rapidly than coding regions. Here we present pairwise comparisons among dicots and monocots for rbcL and two noncoding sequences of cpDNA (the trnL (UAA) intron and the intergenic spacer between the trnL (UAA) 3' exon and the trnF (GAA) gene). It appears that these regions evolve faster (more than three times faster, on average) than rbcL, as previously reported, and that the trnL intron evolves at a rate that is the same as that of the intergenic spacer. By the analysis of these regions, the genera Hordeum, Triticum, and Aegilops clearly could be distinguished. A phylogeny using trnL (UAA) intron sequences is also inferred for some species of the genus Gentiana L., clearly illustrating the phylogenetic utility of these zones at the generic level. The advantages and the disadvantages of the use of these regions to resolve plant phylogenies are discussed, as well as the desirability of a preliminary study before every large-scale analysis.
Response of Cultured Chicken Brain Neuroglial Cells to Infection With Rous Sarcoma Virus2
Authors: Eugene V. Adams
Journal: JNCI Journal of the National Cancer Institute (1966)

Journal Article Response of Cultured Chicken Brain Neuroglial Cells to Infection With Rous Sarcoma Virus Get access Eugene V. Adams Eugene V. Adams Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 37, Issue 3, September 1966, Pages 347–352, https://doi.org/10.1093/jnci/37.3.347 Published: 01 September 1966 Article history Received: 18 February 1966 Published: 01 September 1966
Uncommon Sites of Presentation of Hematologic Malignancies
Authors: Christian Taverna, Peter Vogt, Bernhard C. Pestalozzi
Journal: Journal of Clinical Oncology (1999)

Article Tools DIAGNOSIS IN ONCOLOGY Article Tools OPTIONS & TOOLS Export Citation Track Citation Add To Favorites Rights & Permissions COMPANION ARTICLES No companion articles ARTICLE CITATION DOI: 10.1200/JCO.1999.17.5.1640a Journal of Clinical Oncology - published online before print September 21, 2016 Uncommon Sites of Presentation of Hematologic Malignancies Christian TavernaxChristian TavernaSearch for articles by this author , Peter VogtxPeter VogtSearch for articles by this author , Bernhard C. PestalozzixBernhard C. PestalozziSearch for articles by this author Show More Universitätsspital, Zurich, Switzerland https://doi.org/10.1200/JCO.1999.17.5.1640a First Page Full Text PDF Figures and Tables © 1999 by American Society of Clinical Oncology
Temporal stability of asthma phenotypes identified by a clustering approach: An ECRHS-SAPALDIA-EGEA study
Authors: Valerie Siroux, Anne Boudier, Ivan Curjuric, Xavier Basagagna, Hana Hazgui, Josep Maria Anto, Jean Bousquet, Pierre Olivier Bridevaux, Judith Garcia-Aymerich, Joachim Heinrich, Christer Janson, Nino Künzli, Roberto de Marco, Thierry Rochat, Christian Schindler, Raphaelle Varraso, Isabelle Pin, Nicole Probst-Hensch, Jordi Sunyer, Francine Kauffmann
Journal: European Respiratory Journal (2012)

Background: The temporal stability over time of asthma phenotypes identified using clustering methods has never been addressed.  Aims: To assess whether repeated Latent Class Analysis (LCA) applied in asthma a decade apart leads to the identification of comparable phenotypes, and to characterize the transition between them.  Methods: The LCA was applied twice, 10 years apart, on data from 2399 asthmatic adults recruited in 3 epidemiological surveys using standardized protocols: ECRHS (European Community Respiratory Health Survey, n=1450), SAPALDIA (Swiss cohort study on air pollution and lung disease, n=589) and EGEA (Epidemiological study on Genetics and Environment of Asthma, n=360). 14 variables covering personal characteristics, asthma symptoms, treatment, age of asthma onset, allergic characteristics, lung function and bronchial hyperresponsiveness were considered at both time points.  Results: A model with four latent classes was selected at each time point (prevalence between 14%-36%, mean posterior probability 84%). Two of them were predominantly composed of subjects with active asthma, mainly differing by allergic status and age at onset. Two others were predominantly composed of subjects with inactive-mild asthma, mainly differentiated by allergic status. Most of the population (60%) was assigned to the same asthma phenotype at both time points, although stability varied between phenotypes (from 47% for “active adult-onset asthma” to 68% for “inactive-mild non-allergic asthma”).  Conclusion: Asthma phenotypes identified by a clustering approach 10 years apart were comparable. Further analyses will be conducted using Latent transition analysis.
Case-Control Study of Hair Dye Use by Patients With Breast Cancer and Endometrial Cancer&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: K M Stavraky, E A Clarke, A Donner
Journal: JNCI Journal of the National Cancer Institute (1979)

A case-control study was undertaken of use of permanent and semipermanent hair dyes by women with cancers of several sites, including breast and endometrium. In London, Ontario, 50 cases of of breast cancer and in Toronto 35 cases of breast cancer and 36 cases of endometrial cancer were identified in cancer treatment centers. In London, controls were selected from hospitalized women with diseases other than cancer; in Toronto, controls were selected from women living in the same neighborhood as the patients with cancer. The results did not suggest an increased risk of either breast or endometrial cancer in users of permanent or permanent and semipermanent dyes combined. Although the numbers of cases and controls were small, the consistency of the results for both sites, in both study centers, and the absence of any clear positive relationship between various measures of intensity of use and risk of cancer provided evidence that a large increase in risk was not missed.
Are topical antibiotics an alternative to oral antibiotics for children with acute otitis media and ear discharge?
Authors: Roderick P Venekamp, Vibhore Prasad, Alastair D Hay
Journal: BMJ (2016)

Acute otitis media (AOM) is a common reason for childhood primary care visits and antibiotic prescription in the United Kingdom. 1 2 Many randomised controlled trials (RCTs) have shown that symptoms settle within a few days, irrespective of antibiotic use, 3 with one systematic review reporting that ear pain takes eight days to resolve fully in 90% of children. 4 However observational data and an individual patient data meta-analysis showed that, among children with AOM, those with ear discharge have a worse prognosis 5 and a more prolonged duration of ear pain or fever than those without ear discharge. 6Current guidance from the UK National Institute for Health and Care Excellence recommends that general practitioners consider immediately prescribing oral antibiotics for children presenting with AOM and ear discharge. 7wever, oral antibiotics commonly have side effects such as diarrhoea, vomiting, and rashes 3 and increase the risk of antimicrobial resistance. 8For children with AOM and ear discharge, topical antibiotics are a possible alternative because they put less selective resistance pressure on bacteria and eardrum perforation allows direct entry of the antibiotic into the middle ear, without exposing children to systemic side effects. 9However the risk of ototoxicity is debated. 10 11 What is the evidence of uncertainty?To our knowledge, no RCTs or relevant systematic reviews of the effectiveness of topical antibiotics for children with AOM and ear discharge have been published.
Continuous airway inflammation is related to the development of airway remodeling
Authors: Ryosuke Souma, Kazunori Fukuda, Kentaro Nakano, Mayuko Tanaka, Mari Mizuguchi, Kiyokazu Kikuchi, Kenya Kohyama, Naoto Fueki, Hironori Sagara
Journal: European Respiratory Journal (2012)

In bronchial asthma, airway remodeling leads to refractoriness to treatment. Recent studies suggest that mechanical stress induces remodeling independently of inflammation. For this hypothesis, we examined the effects of continuous mechanical stress and airway inflammation in the mouse.  Mice were divided into 3 groups: an airway inflammation group (group A), a methacholine-inhalation-induced mechanical stress group (group B), and a control group (group C). On days 14 to 29 after sensitization by intraperitoneal injection of ovalbumin, the mice in each group inhaled physiological saline, ovalbumin, or methacholine. Counts of eosinophils and other inflammatory cells, smooth-muscle/ basement-membrane thickening, and goblet-cell hyperplasia were compared among the groups.  Eosinophil counts increased with time in group A, but not in group B or C. Smooth-muscle thickening was slightly greater in group A and group B than in the control group up to day 10 after sensitization. Group A showed a continuous trend toward increased smooth-muscle thickness up to day 15. In contrast, group B showed a slight decrease in smooth-muscle thickness. The difference was more marked in the peripheral than in the central airway. Basement-membrane thickening progressed with time in group A, but was not evident in group B or group C. Goblet-cell hyperplasia calculated on the basis of mucus scores significantly increased in group A, but was unchanged in group B and group C.  Conclusion: Mechanical stress was transiently associated with thickening and proliferation of airway smooth muscle, but this effect decreased with time, suggesting that chronic, continuous airway inflammation plays an important role in remodeling.