tbuckley/cabot-search huggingface dataset:
Interim report of a phase II clinical trial of bevacizumab (Bev) and low dose metronomic oral cyclophosphamide (mCTX) in recurrent ovarian (OC) and primary peritoneal carcinoma: A California Cancer Consortium Trial
Authors: A. A. Garcia, A. M. Oza, H. Hirte, G. Fleming, D. Tsao-Wei, L. Roman, S. Swenson, D. Gandara, S. Scudder, R. Morgan
Journal: Journal of Clinical Oncology (2005)

5000 Background: Bev is a recombinant humanized anti-VEGF monoclonal antibody that inhibits the growth of a number of human cancers, including ovarian cancer. Low dose chronic chemotherapy (metronomic chemotherapy) inhibits angiogenesis. In preclinical models enhanced antitumor activity has been observed with the combination of anti-VEGF antibodies and metronomic chemotherapy. Methods: We developed a 2-stage phase II study to evaluate the activity and toxicity profile of the combination of Bev and mCTX in recurrent OC and to explore serologic markers of angiogenesis and genetic polymorphisms as potential surrogate markers of response and/or toxicity. Bev 10 mg/m2 i.v. was administered on days 1, 8 and 15 and then every 2 weeks with CTX 50 mg po qd. Patients were required to have uni-dimensionally measurable disease, recurrence after platinum and paclitaxel chemotherapy, 0–2 chemotherapy regimens for recurrent disease and performance status 0–2. Results: 29 patients have been enrolled and are evaluable for response. Median age 57 (39–83). Prior chemotherapy included: platinum and paclitaxel (100%), liposomal doxorubicin (31%), topotecan (31%). Grade 3–4 toxicities include: pain (6), hypertension (3), hyponatremia (3), urinary (2), fatigue (2), lymphopenia (2), gastrointestinal obstruction (2), and increased transaminases, thrombosis, prolonged PTT, CNS ischemia, hyperglycemia, hypomagnesemia, edema, hot flashes, pulmonary and arthritis (1 each). No treatment related deaths. Median number of courses 4 (range 2–9). Best response: 6 PR (21%), 17 SD (59%) and 6 PD (21%). Median PFS 5.8 months (95% CI 3.8–8.1), PFS at 6 months 47% (± 11%). Conclusions: Based on the encouraging response rate and 6 month PFS the second stage of accrual was opened. Correlation with serologic markers and genetic polymorphisms is ongoing. The combination of Bev and mCTX shows encouraging activity in recurrent ovarian cancer. Supported in part by NCI N01 CM17101 Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Genentech
Megace and no diabetes mellitus. (Letter)
Authors: Ansfield Fj
Journal: Annals of Internal Medicine (1977)

For the past 4 years this author has treated almost 300 patients with Megace (megestrol acetate) for periods ranging from 6 weeks to 18 months and in a few instances longer.  Most of the patients received Megace alone with the remaining group receiving it in combination with 4 other compounds.  The development of diabetes mellitus as described in the paper by J.C. Bottino and C.K. Tashima was not observed in any patients.  The majority of patients had SMA 12/60 profiles at 6-week intervals during the 1st several months on therapy and later at about 2-month intervals including blood sugars.  The several patients who had controlled adult diabetes when placed on Megace therapy alone or in combination developed no exacerbation of their diabetes while on this steroid.  All of the patients received 40 mg 4 times daily throughout the period they were on Megace.  It is this authors opinion that in the case described by Bottino and Tashima the development of diabetes mellitus was simply coincidental.  This opinion is based on the treatment of a large number of patients with this compound.
The transcriptomic landscape and directed chemical interrogation of MLL-rearranged acute myeloid leukemias
Authors: Vincent-Philippe Lavallée, Irène Baccelli, Jana Krosl, Brian Wilhelm, Frédéric Barabé, Patrick Gendron, Geneviève Boucher, Sébastien Lemieux, Anne Marinier, Sylvain Meloche, Josée Hébert, Guy Sauvageau
Journal: Nature Genetics (2015)
Functional imaging using DCE-US: Which parameter for the early evaluation of antiangiogenetic therapies?
Authors: N. Lassau, S. Koscielny, M. Chebil, L. Chami, R. Bendjilali, A. Roche, B. Escudier, A. LeCesne, J. Soria
Journal: Journal of Clinical Oncology (2009)

3524 Background: The early evaluation of anti-angiogenic treatments is a challenge in oncology. Functional imaging methods based on the measure of tumoral vascularization have been developed using different modalities (CT, MRI, US). We analyzed the response in four studies using different targeted treatments with dynamic contrast enhanced-ultrasonography (DCE-US). Seven parameters characterizing tumoral perfusion were estimated. The objective of the study was to determine which parameter is the most appropriate to confirm earlier the efficacy of treatments. Methods: A total of 823 DCE-US were performed in 117 patients included in 4 following studies (multikinase inhibitor targeting angiogenic-receptor with a cytotoxic or thyrosine-kinase inhibitor targeted angiogenic-receptor and C-kit or monoclonal antibody anti-VEGFR). Each DCE-US was performed using contrast agent (Sonovue, Bracco) with perfusion and quantification softwares (Toshiba) from raw linear data with a high temporal resolution: 4 frames per second during 3 minutes. Seven quantitative parameters of perfusion were estimated: peak intensity (PI) and area under the total curve (AUC), area under the wash-in (AUWI), area under the wash-out (AUWO), time to peak intensity, mean transit time (MTT), wash-in slope. DCE-US were performed before treatment and after D3, D 8, 15, 21 (according each study design) and every 2 months. Patients were classified in good responders and bad responders according the response (RECIST on CT-scan) after 2 cycles or 2 months. Results: Among the 7 parameters, 2 parameters related to the blood volume studies (AUC and AUWO) were always earlier significantly modified (p = 0.04 to p = 0.004). One was never modified: MTT. For the 4 others, it's depending of each study. Conclusions: DCE-US appears as a sensitive tool to evaluate tumoral response to anti-angiogenic drugs. Functional parameters related to the blood volume are more pertinent and represent a key add value to early evaluation of these therapies studies. No significant financial relationships to disclose.
The p15ink4B tumor suppressor is a direct target for the ZNF217 oncoprotein
Authors: Gobi Thillainadesan
Journal: Cancer Research (2008)

2779   ZNF217 is a kruppel-like transcription factor and candidate oncogene that is amplified and overexpressed in multiple cancer cell lines and tumours and recent evidence indicates that ZNF217 overproduction results in abnormal cell growth. ZNF217 is a major constituent of a transcriptional complex containing chromatin-modifying activities known to promote transcriptional repression and include the repressor CoREST, the histone deacetylase 2 (HDAC2) that catalyzes removal of acetyl groups from conserved lysines on histones, lysine demethylase I (LSD1) which removes mono- or di-methyl groups on lysine 4 of histone H3 (H3K4), and the C terminal binding protein (CtBP). In this study we have combined (1) genome wide expression profiling of cancer cells in which ZNF217 has been downregulated using siRNA and (2) chromatin immunoprecipitation (ChIP) in conjunction with DNA selection and ligation (ChIP-DSL), to identify genes directly regulated by ZNF217 in MCF7 breast cancer cells. Our results indicate that the tumour suppressor p15ink4b is a direct target of the ZNF217 complex. Furthermore ZNF217, CoREST and LSD1 are all highly enriched within a region of the promoter that is essential for activation of p15INK4B. To determine whether silencing of p15INK4B is dependent on the ZNF217 complex, we transfected MCF-7 cells with siRNA targeting either ZNF217 or LSD1 and ink4b expression was monitored by realtime PCR or western blotting. A dramatic increase in p15INK4B expression was observed providing strong evidence that the ZNF217 complex is a key repressor of the p15INK4B gene in MCF7 cells. Importantly, the identification of the ink4b gene as a direct target for the ZNF217 corepressor complex represents a potentially novel link between amplification of ZNF217 and the loss of TGFβ responsiveness in breast cancer.
Cannabidiol in patients with treatment-resistant epilepsy: an open-label interventional trial
Authors: Orrin Devinsky, Eric Marsh, Daniel Friedman, Elizabeth Thiele, Linda Laux, Joseph Sullivan, Ian Miller, Robert Flamini, Angus Wilfong, Francis Filloux, Matthew Wong, Nicole Tilton, Patricia Bruno, Judith Bluvstein, Julie Hedlund, Rebecca Kamens, Jane Maclean, Srishti Nangia, Nilika Shah Singhal, Carey A Wilson, Anup Patel, Maria Roberta Cilio
Journal: The Lancet Neurology (2015)
FRI0625-HPR The Patients' Perspective on Nurse-Led Screening for Cardiovascular Risk in Rheumatoid Arthritis: A Qualitative Focus Group Interview Study
Authors: J.C. Froelund, J. Primdahl
Journal: Annals of the Rheumatic Diseases (2015)

<h3>Background</h3> Patients with Rheumatoid Arthritis (RA) have an increased morbidity and mortality due to cardiovascular disease (CVD) and screening for cardiovascular risk is recommended by EULAR (European League Against Rheumatism) (1). There is a lack of evidence on RA patients9 experience of being screened for CVD, which is important in order to determine how to organize and further develop screening programs for CVD amongst patients with RA. <h3>Objectives</h3> To explore RA patients9 experiences from participation in nurse-led screening for CVD and to identify key issues on to how to organize future screening programs. <h3>Methods</h3> Three qualitative focus group interviews with 14 outpatients (eight female and six men; age ranged from 51-70 years) diagnosed with RA were carried out. The participants were stratified into groups depending on whether the participant had low to moderate or high 10-year risk of cardiovascular death according to the European SCORE system (2). Data was analyzed using meaning condensation (3) in accordance with a phenomenological approach in order to identify key themes. <h3>Results</h3> Five main themes were identified: Reactions to receiving the invitation to the screening consultation; screening consultations were adjusted to needs and RA; time was aligned with needs; the screening consultation lead to relief; motivation and a sense of control. Regardless of their CV risk the participants found it important that the screening consultation were adjusted to their needs and RA, as RA had a major impact on their daily life. <h3>Conclusions</h3> Nurse-led screening consultations can lead to relief, motivation and a sense of control. When planning future screening programs for CVD amongst patients with RA it is important that the screening consultation is individualised and tailored to the patients9 needs and their RA. <h3>References</h3> Peters MJ, Symmons DP, McCarey D, Dijkmans BA, Nicola P, Kvien TK, et al. EULAR evidence-based recommendations for cardiovascular risk management in patients with rheumatoid arthritis and other forms of inflammatory arthritis. Ann Rheum Dis 2010 Feb;69(2):325-31. Graham I, Atar D, Borch-Johnsen K, Boysen G, Burell G, Cifkova R, et al. European guidelines on cardiovascular disease prevention in clinical practice: full text. Fourth Joint Task Force of the European Society of Cardiology and other societies on cardiovascular disease prevention in clinical practice (constituted by representatives of nine societies and by invited experts). Eur J Cardiovasc Prev Rehabil 2007 Sep;14 Suppl 2:S1-113. Giorgi A. An application of phenomenological method in psychology. Giorgi,A; Fischer,C; Murray,E. Dupuesne studies in phenomenological psychology. Pittsburg, PA: Duquesne University Press 1975 Jan;2:82-103. <h3>Disclosure of Interest</h3> None declared
Abstract 18062: Neonatal Outcomes and Maternal Morbidity Associated With Pregnancy in Women with Congenital Heart Disease
Authors: Camden Hebson, Dan Lin, Turgay Ayer, Jan Vlachy, Martina Badell, Marissa Platner, Agasha Katabarwa, Julia Shinnick, Anurag Sahu, Wendy Book
Journal: Circulation (2014)

Background: Women with congenital heart disease (WCHD) who are considering pregnancy need counseling regarding maternal and offspring risk. Previous studies have not focused on neonatal outcomes and have mostly described lower risk patients. Methods and Results: We enrolled 113 WCHD (mean age 32 ± 5 years, 51% with NYHA functional class >1, 28% with World Health Organization (WHO) risk class > 2, 81% with moderate or higher CHD complexity) in our study and reviewed the medical record for their baseline cardiac status as well as their post-natal outcomes. We compared our cohort to a demographically similar cohort of patients (n = 147) without CHD. Neonatal outcomes included prematurity (< 37 weeks gestation), admission to the NICU, low birth weight (< 2.5 kg), and neonatal death, while maternal outcomes were arrhythmias, heart failure, stroke, and death. Significant predictors of neonatal complications included history of cyanotic CHD (OR 3.1, CI 1.0-9.7, p = 0.04), need for cardiac medications (OR 3.2, CI...
Phase I experience with an anti-glycotope monoclonal antibody, RAV12, in recurrent adenocarcinoma
Authors: H. A. Burris, N. Lewis, L. S. Rosen, S. F. Jones, R. B. Cohen, L. A. Kunkel, S. J. Stewart
Journal: Journal of Clinical Oncology (2007)

14017 Background: RAV12 is a high affinity, internalizing, chimeric IgG 1 monoclonal antibody (MAb) that binds RAAG12, a novel primate-restricted N-linked carbohydrate epitope present on multiple cell-surface proteins. RAAG12 is variably expressed on normal non-keratinizing epithelia, particularly those of GI origin (cytoplasm and apical membrane), and is not expressed on human tissues from the cardiovascular, endocrine, hematolymphatic, neuromuscular, and central nervous systems. IHC studies demonstrated diffuse membrane staining on &gt; 90% of human colorectal, gastric, and pancreatic adenocarcinoma samples. RAAG12 is distinct from previously reported mucin or Lewis blood group carcinoma-associated carbohydrates. In vitro, RAV12 kills tumor cells by oncosis and facilitates ADCC. Methods: In December 2004, a phase I dose-escalation safety and pharmacokinetics (PK) trial was begun in patients with recurrent (1 to 3 prior treatments) adenocarcinoma. RAV12 was administered weekly x 4, twenty-eight patients have received treatment in the following cohorts: 0.3 mg/kg qw (6), 1.0 mg/kg qw (8), 1.5 mg/kg qw (7), 0.5 mg/kg biw (3), 0.75 mg/kg biw (2), and 0.5 mg/kg tiw (2). Sixteen patients had colorectal, 5 gastroesophageal, 4 pancreatic, 2 lung cancer, and 1 breast cancer. Responses were evaluated on day 42. Results: Preliminary analysis demonstrated dose-dependent PK. Three clinical syndromes associated with drug administration have been observed to date: 1) abdominal cramping pain (21 patients) and diarrhea (18 patients) particularly at the higher doses, 2) asymptomatic, self-limited, generally rapidly reversible excursions of liver function tests (16 patients), and 3) asymptomatic, self-limited, rapidly reversible excursions of pancreatic enzymes (6 patients). One patient (0.3 mg/kg qw), with advanced pancreatic cancer, had a &gt; 50% reduction in CA19–9, continued treatment, and had TTP &gt; 5 months. One patient with colorectal cancer (1.5 mg/kg qw) experienced a durable partial remission, continued treatment, and had TTP &gt; 8 months. Conclusions: RAV12 has activity in recurrent adenocarcinoma. Side effects uncommonly have been dose limiting. The trial continues to define dose/schedule to be recommended for phase 2 testing. No significant financial relationships to disclose.
The mannose receptor negatively modulates the Toll-like receptor 4–aryl hydrocarbon receptor–indoleamine 2,3-dioxygenase axis in dendritic cells affecting T helper cell polarization
Authors: Fabián Salazar, Laurence Hall, Ola H. Negm, Dennis Awuah, Patrick J. Tighe, Farouk Shakib, Amir M. Ghaemmaghami
Journal: Journal of Allergy and Clinical Immunology (2015)
Tomotherapy-based IMRT after limb-preserving surgery for extremity soft-tissue sarcomas: Planning, verification, and treatment times.
Authors: R. E. Carr, E. Stockley, D. Lee, M. Wilkinson, J. H. Mott
Journal: Journal of Clinical Oncology (2010)

e20514 Background: Radiotherapy improves local control after limb-sparing surgery for soft tissue sarcomas (STS). IMRT can optimize treatment dose conformity compared to standard conformal therapy. At the Northern Centre for Cancer Care we prescribe 60Gy. Until 2009 this was delivered using conventional Linac-based 3D conformal RT. Since installation of a tomotherapy unit, because of the potential long- term clinical advantages, selected sarcoma patients have been treated with postoperative IMRT. Tomotherapy necessitates longer planning, verification, and treatment times. These have been analysed to assess impact on resources. Methods: Six such patients have now been treated with IMRT. Tomotherapy planning requires more volume definition of organs at risk and “help structures” and processing for dose optimization. Times have been recorded within the implementation phase. Conventional Linac verification uses portal imaging daily for three days. Shifts are made to exclude systematic error, if tolerance is exceeded, and prompts further daily checks. Otherwise checks are weekly. Tomotherapy uses MV-CT and software uses bone and soft-tissue levels to auto-match current and planned positions. It suggests 4 shifts, Lat., Long., Vert. and Roll, which can be corrected on-set. The radiographers check whether the suggested corrections are optimal, and record actual shifts. Verification is applied daily. Results: See Table. Conclusions: Tomotherapy planning takes three to four times longer than conventional planning, and currently limits patients allocated to IMRT. Treatment delivery times are longer, but a large component of this arises from daily verification. Average planning times (mins) Target vol. definition Definition of other structures Planning Approval Senior check Extra QA Total Conformal linac RT 30-60 30 100 15 65 240-270 Tomotherapy IMRT 30-60 120ü to 180 Batch prep 60 Optimize 180-360 30 120 90 630-900 Patient number Average daily verification time (mins) Lat shift Long shift Vert shift Roll Beam on time 1 11 1.21 −2.28 5.05 −0.22 7 2 14.3 −4.8 −5.4 11.13 −0.17 9.4 3 16 −5.65 0.64 4.94 1.44 8.1 4 15 2.62 −4.35 15.36 −0.72 7.7 5 15 −0.58 −4.15 6.88 0.31 10.2 6 11 −0.27 −1.52 12.17 0.13 6.4 No significant financial relationships to disclose.
Smoking and adult glioma: a population-based case-control study in China
Authors: Lei Hou, Jingmei Jiang, Boqi Liu, Wei Han, Yanping Wu, Xiaonong Zou, Philip C. Nasca, Fang Xue, Yuanli Chen, Biao Zhang, Haiyu Pang, Yuyan Wang, Zixing Wang, Junyao Li
Journal: Neuro-Oncology (2015)

Smoking increases the risk of numerous cancers; however, an association of smoking with adult gliomas has not been found in a population. This case-control study included 4556 glioma cases (ICD-9 code 191.0–191.9) aged ≥30 years and 9112 controls from a national survey of smoking and mortality in China in 1989–1991. Controls from 325 255 surviving spouses of all-cause deaths were randomly assigned to cases in each of 103 areas according to sex and age groups at a ratio of 2:1. Smoking information was ascertained retrospectively by interviewing surviving spouses. After adjustment for confounders, smoking increased the risk of glioma deaths by 11% (odds ratio [OR] = 1.11; 95% confidence interval [CI]: 1.03–1.21). Compared with non-smokers; the increased risk was 9% (OR = 1.09; 95% CI: 0.99–1.20) in men and 16% (OR = 1.16; 95% CI: 1.00–1.36) in women. The risk increased with age and doses. For individuals aged ≥50 years, smoking was associated with higher risk of glioma death by 25% (OR = 1.25; 95% CI: 1.15–1.38); this increased risk for smokers who smoked ≥20 cigarettes daily for ≥30 years was 53% (OR = 1.53; 95% CI: 1.34–1.74). There were similar findings in both men and women and with either pathology-based or non–pathology-based comparisons. This study indicates that smoking is associated with glioma deaths in the Chinese population. Long-term heavy smoking could be a factor for risk stratification in individuals attending brain tumor clinics.
Pazopanib in pretreated advanced neuroendocrine tumors: a phase II, open-label trial of the Spanish Task Force Group for Neuroendocrine Tumors (GETNE)
Authors: E. Grande, J. Capdevila, D. Castellano, A. Teulé, I. Durán, J. Fuster, I. Sevilla, P. Escudero, J. Sastre, J. García-Donas, O. Casanovas, J. Earl, L. Ortega, M. Apellaniz-Ruiz, C. Rodriguez-Antona, T. Alonso-Gordoa, J.J. Díez, A. Carrato, R. García-Carbonero
Journal: Annals of Oncology (2015)
The impact of β-adrenergic signaling on radioresistance and anti-tumor immunity
Authors: Mark Bucsek, Lauren Evans, Timothy Winslow, Bonnie L Hylander, Anurag Singh, Elizabeth Repasky
Journal: Journal for ImmunoTherapy of Cancer (2015)

Meeting abstracts Our laboratory has demonstrated that mildly cool housing temperatures, (a stress known to be mediated by sympathetic nerve activity and β-adrenergic receptors) can significantly enhance the incidence, growth, and metastasis of tumors in murine models by suppressing anti-tumor
Factors influencing accrual to ACOSOG Z0011, a randomized phase III trial of axillary dissection vs. observation for sentinel node positive breast cancer
Authors: A. M. Leitch, L. McCall, P. Beitsch, P. Whitworth, D. Reintgen, P. Blumencranz, S. Saha, T. Bauer, K. K. Hunt, A. Giuliano
Journal: Journal of Clinical Oncology (2006)

601 Background: The American College of Surgeons Oncology Group opened a phase III randomized trial to assess the value of axillary node dissection (ALND) after positive sentinel node biopsy (SNB). After 5.5 years, the trial closed due to poor accrual with only 891 patients of the planned 1900 accrued. The purpose of the current analysis is to assess factors impacting accrual to Z0011. Methods: Women having SNB for T1 or T2 breast cancer were eligible for participation in the Z0010 trial to assess the significance of micrometastases identified by immunohistochemistry. If the SN was positive for metastasis by H&amp;E, the patient was eligible for randomization on Z0011 trial. Intraoperative (IOR) and postoperative randomization were allowed. Patients having SNB outside of the Z0010 trial were eligible. Results: 1003 patients from the Z0010 trial were eligible for randomization on Z0011. Of these, only 37% were entered in Z0011. Z0010 participants accounted for 42% of patients in Z0011. 16% of patients not randomized refused ALND. 69% of those not randomized had ALND. 67% of these had no additional positive nodes. Only 14% had ≥ 4 positive nodes. Enrollment of eligible Z0010 patients varied by type of institution: 25% at academic sites, 42% at teaching affiliated and 53% at community (p &lt; 0.0001). By geographic region, sites in the South entered 42% of eligible patients compared with 24–36% in other geographic regions (p=0.0027). Only 32% of patients were consented for IOR based on frozen section of the SN. Sites in the South and West were less likely to use IOR (25% and 28%) compared to Northeast and Midwest (45% and 46%) (p &lt; 0.0001). 110 sites participated in Z0011, yet 48% of patients were enrolled by 10% of sites. Conclusions: Failure of this important trial to accrue as planned is likely related to the clinical bias of physicians and patients to standard ALND. Yet, 2/3 of patients had no additional positive nodes and extensive nodal disease was infrequent. While it was thought that IOR might improve accrual to Z0011, the most successful sites were less likely to use this approach. Community surgeons were most successful in randomizing patients. [Table: see text]
P1351 : An open-label study to evaluate the efficacy and safety of co-formulated ombitasvir/paritaprevir/ritonavir with ribavirin in adults with chronic HCV genotype 4 infection in Egypt
Authors: W. Doss, G. Esmat, R.B. Qaqish, I. Waked, G. Shiha, A. Yosry, J. King, C. Hall, N. Mobashery
Journal: Journal of Hepatology (2015)