tbuckley/cabot-search huggingface dataset:
Ovarian Suppression With Triptorelin During Adjuvant Breast Cancer Chemotherapy and Long-term Ovarian Function, Pregnancies, and Disease-Free Survival
Authors: Matteo Lambertini, Luca Boni, Andrea Michelotti, Teresa Gamucci, Tiziana Scotto, Stefania Gori, Monica Giordano, Ornella Garrone, Alessia Levaggi, Francesca Poggio, Sara Giraudi, Claudia Bighin, Carlo Vecchio, Mario Roberto Sertoli, Paolo Pronzato, Lucia Del Mastro
Journal: JAMA (2015)

Whether the administration of luteinizing hormone-releasing hormone analogues (LHRHa) during chemotherapy is a reliable strategy to preserve ovarian function is controversial owing to both the lack of data on long-term ovarian function and pregnancies and the safety concerns about the potential negative interactions between endocrine therapy and chemotherapy.To evaluate long-term results of LHRHa-induced ovarian suppression during breast cancer chemotherapy.Parallel, randomized, open-label, phase 3 superiority trial conducted at 16 Italian sites. Between October 2003 and January 2008, 281 premenopausal women with stage I to III hormone receptor-positive or hormone receptor-negative breast cancer were enrolled. Last annual follow-up was June 3, 2014.Patients were randomized to receive adjuvant or neoadjuvant chemotherapy alone (control group) or chemotherapy plus triptorelin (LHRHa group).The primary planned end point was incidence of chemotherapy-induced early menopause. Post hoc end points were long-term ovarian function (evaluated by yearly assessment of menstrual activity and defined as resumed by the occurrence of at least 1 menstrual cycle), pregnancies, and disease-free survival (DFS).A total of 281 women (median age, 39 [range, 24-45] years) were randomized. Median follow-up was 7.3 years (interquartile range, 6.3-8.2 years). The 5-year cumulative incidence estimate of menstrual resumption was 72.6% (95% CI, 65.7%-80.3%) among the 148 patients in the LHRHa group and 64.0% (95% CI, 56.2%-72.8%) among the 133 patients in the control group (hazard ratio [HR], 1.28 [95% CI, 0.98-1.68]; P = .07; age-adjusted HR, 1.48 [95% CI, 1.12-1.95]; P = .006). Eight pregnancies (5-year cumulative incidence estimate of pregnancy, 2.1% [95% CI, 0.7%-6.3%]) occurred in the LHRHa group and 3 (5-year cumulative incidence estimate of pregnancy, 1.6% [95% CI, 0.4%-6.2%]) in the control group (HR, 2.56 [95% CI, 0.68-9.60]; P = .14; age-adjusted HR, 2.40 [95% CI, 0.62-9.22]; P = .20). Five-year DFS was 80.5% (95% CI, 73.1%-86.1%) in the LHRHa group and 83.7% (95% CI, 76.1%-89.1%) in the control group (LHRHa vs control: HR, 1.17 [95% CI, 0.72-1.92]; P = .52).Among premenopausal women with either hormone receptor-positive or hormone receptor-negative breast cancer, concurrent administration of triptorelin and chemotherapy, compared with chemotherapy alone, was associated with higher long-term probability of ovarian function recovery, without a statistically significant difference in pregnancy rate. There was no statistically significant difference in DFS for women assigned to triptorelin and those assigned to chemotherapy alone, although study power was limited.clinicaltrials.gov Identifier:NCT00311636.
The influenza A(H5N1) epidemic at six and a half years: 500 notified human cases and more to come
Authors: A Tarantola, P Barboza, V Gauthier, S Ioos, N El Omeiri, M Gastellu-Etchegorry, Collective for the Epidemic Intelligence team at InVS
Journal: Eurosurveillance (2010)

Binary file ES_Abstracts_Final_ECDC.txt matches
Impact of Consolidation Radiotherapy in Patients With Advanced Breast Cancer Treated With High-Dose Chemotherapy and Autologous Bone Marrow Rescue
Authors: Dennis L. Carter, Lawrence B. Marks, Joseph M. Bean, Gloria Broadwater, Atif Hussein, James J. Vredenburgh, William P. Peters, Leonard R. Prosnitz
Journal: Journal of Clinical Oncology (1999)

To examine the impact of consolidation radiotherapy (RT) after high-dose chemotherapy with autologous bone marrow rescue (HDC) in patients with advanced breast cancer.Between 1988 and 1994,425 patients with metastatic or recurrent breast cancer received doxorubicin, fluorouracil, and methotrexate (AFM) induction chemotherapy in a single-institution prospective trial. One hundred patients who achieved a complete response were randomized to receive HDC (cyclophosphamide, cisplatin, carmustine), with autologous bone marrow rescue immediately after AFM, or to observation, with HDC to be administered at next relapse. Seventy-four of the 100 became eligible for RT; 53 received consolidation RT (HDC RT+ and 21 did not (HDC RT-). The assignment of RT was not randomized. The RT+ and RT- groups were similar with regard to number of involved sites, the fraction of patients with only local-regional disease, age, and interval since initial diagnosis. Local control at previously involved sites and distant sites was assessed with extensive radiologic and clinical evaluations at the time of first failure or most recent follow-up. The impact of RT on failure patterns, event-free survival, and overall survival was evaluated.Sites of first failure were located exclusively at previously involved sites in 28% of RT+ patients versus 62% of RT- patients (P < .01). Event-free survival at 4 years was 31% and 21% in the RT+ and RT-groups, respectively (P = .02). Overall survival at 4 years was 30% and 16% in the RT+ and RT- groups, respectively (P = .20).Patients with advanced breast cancer who were treated with HDC without RT failed predominantly at the initial sites of disease. The addition of RT appeared to reduce the failure rate at initial disease sites and may improve event-free and overall survival. Our observations await verification in a trial in which assignment to RT is randomized.
The Paradox of Hypoxic and Oxidative Stress in Atherosclerosis⁎⁎Editorials published in the Journal of the American College of Cardiology reflect the views of the authors and do not necessarily represent the views of JACC or the American College of Cardiology.
Authors: Manuel Mayr, Anissa Sidibe, Anna Zampetaki
Journal: Journal of the American College of Cardiology (2008)
BMS-354825 multiple oncogenic tyrosine kinase inhibitor induces cell cycle arrest and apoptosis of head and neck squamous cell carcinoma (HNSCC) and non-small cell lung cancer (NSCLC) cells
Authors: Faye M. Johnson, Babita Saigal, Moshe Talpaz, Nicholas J. Donato
Journal: Cancer Research (2005)

674   BMS-354825 is an ATP-competitive, small molecule tyrosine kinase inhibitor that suppresses Src family kinases, EphA2, Abl, c-kit, and PDGFR activity at sub-nanomolar concentrations. Src activation in malignant cells induces pleiotropic effects that include transformation, increased proliferation, enhanced survival, stimulation of angiogenesis, and changes in motility. Src is overexpressed and activated in epithelial tumors, including HNSCC and NSCLC. Levels of expression or activation correlate with disease progression, suggesting that Src inhibition may have therapeutic activity in these diseases. HNSCC and NSCLC incubation with clinically relevant BMS-354825 concentrations has multiple biological effects that appear to be mediated through Src and/or EphA2 inhibition. BMS-354825 inhibited migration in all cell lines and induced cell cycle arrest (block in the G1 to S transition) and subsequent apoptosis in highly sensitive cell lines. The effects on migration correlate with inhibition of Src and downstream mediators of adhesion (FAK, p130, paxillin), while cell cycle effects and apoptosis correlate with inhibition of AKT, induction of p27, and de-phosphorylation of Rb. BMS-354825 also induced morphology changes that were integrin-dependent, consistent with an upstream role for Src in regulation of focal adhesion complexes. Additional studies are focused on the effects Src inhibition on angiogenesis and metastasis in animal models of aerodigestive tract tumors. BMS-354825 may have therapeutic activity against HNSCC and NSCLC.
AZD9291, a mutant-selective EGFR inhibitor, as first-line treatment for <i>EGFR</i> mutation-positive advanced non-small cell lung cancer (NSCLC): Results from a phase 1 expansion cohort.
Authors: Suresh S. Ramalingam, James Chih-Hsin Yang, Chee Khoon Lee, Takayasu Kurata, Dong-Wan Kim, Thomas John, Naoyuki Nogami, Yuichiro Ohe, Yuri Rukazenkov, Paul Frewer, Mireille Cantarini, Serban Ghiorghiu, Pasi A. Janne
Journal: Journal of Clinical Oncology (2015)

8000 Background: AZD9291 is an orally administered EGFR TK inhibitor with activity against the sensitizing EGFR mutations (EGFRm) and the T790M resistance mutation. It has demonstrated anticancer activity in patients with EGFR-TKI pre-treated EGFRm T790M positive advanced NSCLC. Methods: Treatment-naïve patients with EGFRm advanced NSCLC received AZD9291 at doses of 80 mg/day or 160 mg/day (sequential cohorts) in the first-in-human phase I study (AURA, NCT01802632). EGFRm status was tested locally at the treating site and/or confirmed by central testing (cobas EGFR mutation test). Salient eligibility included presence of measurable disease, WHO performance status of 0 or 1, and acceptable organ function. Stable brain metastases were permitted. The objective of these cohorts was to investigate safety, tolerability, and anticancer activity of AZD9291 in the first-line EGFRm treatment setting. Results: Sixty patients were enrolled (30 each in 80 mg and 160 mg dose cohorts). Patient baseline characteristics: median age 63.5; male 25%; WHO performance status 0.57%, 1.43%; Asian 72%, and white 23%; central mutation test result exon 19 del 37%, L858R 40%, other EGFR sensitizing mutations 3%, T790M 8%. At the data-cutoff of 2 December 2014, 52 out of 60 patients remain on study treatment with a median treatment exposure of 260 days and 171 days for 80 mg and 160 mg cohorts, respectively. The objective response rate was 70% (95% CI 57, 81): 80 mg, 60%; 160 mg, 80% and the median progression-free survival (PFS) has not been reached. The disease control rate was 97% (95% CI 89, 100): 80 mg, 93%; 160 mg, 100%. Overall, the 3- and 6-month PFS rates were 93% and 87%, respectively (7/60 events, 12% mature). Grade ≥ 3 AEs were reported by 33% of patients. The incidences of grade 3 skin rash and diarrhea for the two dose cohorts combined were 1/60 and 2/60, respectively. Conclusions: AZD9291 has a manageable tolerability profile and is associated with promising anticancer activity as first-line treatment of EGFRm advanced NSCLC. A Phase III study to compare AZD9291 to erlotinib or gefitinib has been initiated (NCT02296125). Clinical trial information: NCT01802632.
Abstract 14774: Rescue of Diabetes-related Impairment of Ischemia-mediated Neovascularization With Fenofibrate Treatment
Authors: Kushwin Rajamani, Jun Yuan, Laura Lecce, Alicia Jenkins, Anthony Keech, Martin Ng
Journal: Circulation (2014)

Background: Fenofibrate, a PPARα agonist, reduced amputation events in the Fenofibrate Intervention and Event Lowering in Diabetes study among 9795 patients, the mechanisms of which are unknown. We hypothesised that fenofibrate may attenuate diabetes-related impairment in ischemia-mediated neovascularization. Methods: Hindlimb ischemia was induced in a murine model of streptozotocin induced diabetes mellitus (DM) in wildtype and PPARα receptor knockout mice (KO) with/without fenofibrate (30mg/kg/day in high fat diet). Ischemic recovery was assessed by laser doppler, foot movement and capillary density analysis. Key angiogenic events (tubulogenesis) and expression of thioredoxin-interacting protein (TXNIP) mRNA and protein following normal and high glucose (5 vs 25mM glucose) environments were determined in cultured endothelial cells (ECs), with/without selective PPARα receptor antagonist (10μM MK886) and agonist (10μM WY14643). Results: DM profoundly impaired blood flow recovery following hindlimb ischemia (0.51±0.04[n=5] vs 0.34±0.03[n=5];p&lt;0.001). Fenofibrate (FF) restored DM-related impairment in blood flow recovery (0.53±0.04[n=5] vs 0.34±0.03[n=5];p&lt;0.01), capillary density (1.48±0.03 vs1.20±0.04;p&lt;0.01), foot movement scores to levels of non-diabetic controls. Similar findings for fenofibrate were observed in diabetic PPARα KO mice. In vitro, fenofibric acid (FA) rescued hyperglycemia-induced impairment in EC tubulogenesis (87.8 vs 58.3% of control;p&lt;0.05) by a PPARα-independent mechanism. FA prevented hyperglycemia-induced overexpression of TXNIP (mRNA: 1.20±0.16 vs 1.84±0.28 folds of control;p&lt;0.01) an exquisitely glucose-sensitive regulator of angiogenesis, in a PPARα-independent manner. Furthermore, overexpression of TXNIP abrogated the protective effects of FA. Conclusions: Fenofibrate rescues diabetic impairment in ischemia-mediated angiogenesis via a largely PPARα-independent mechanism. Improved neovascularization may therefore explain in part the reduced amputations seen with fenofibrate in type 2 diabetes. These findings provide a novel mechanistic understanding for fenofibrate action and may provide a platform for new drug targets.
Time to bust the myth?
Authors: Roy J Shephard
Journal: British Journal of Sports Medicine (2015)

Recent editorials have renewed the debate over the possible contribution of a secular decrease in habitual physical activity to the current obesity epidemic.1 ,2 In arguing against the role of physical inactivity, Malhotra et al 1 cite a widely criticised opinion piece3 ,4 suggesting there has been “little change of physical activity levels in the past 30 years.” Blair2 counters that although leisure activity may not …
A Phase III Trial of Postoperative Chemotherapy or No Further Treatment for Patients with Node- Negative Stage I-Ii Intermediate or High Risk Endometrial Cancer. Engot-En2-Dgcg / Eortc 55102
Authors: F. Amant, C. Lundgren, F. Kridelka, A. Ferrero, S. Greggi, P.T. Soliman, M.R. Mirza
Journal: Annals of Oncology (2014)
Impact of early lung cancer detection on surgical mortality
Authors: U. Pastorino, P. Borasio, P. Solli, M. Bellomi, C. Fava, F. Leo, S. Novello, G. Scagliotti
Journal: Journal of Clinical Oncology (2004)

7047 Background: Pilot studies in high risk individuals have shown that spiral CT can detect early cancer, with high resectability rate and nearly 80% stage I disease. However, concern has been raised that competing risks of death and screening-related mortality may overcome the benefits of early detection. To evaluate the impact of early lung cancer detection on peri-operative mortality, we compared the death rate in the first Italian early detection project with a consecutive series of lung cancers resected in the same institutions and period of time. Methods: In 2000, a pilot trial was launched at the European Institute of Oncology of Milan and the S.Luigi Hospital of Orbassano, to test the value of annual low-dose CT and positron emission tomography (PET) in a cohort of 1555 volunteers, aged 50 years or older who had smoked for 20 pack-years or more. A total of 1396 lung cancer resections, performed after standard detection in the same two institutions from 1998 to 2002, were analysed as control group. Results: At the end of 2002, 33 lung cancers were diagnosed through the early detection project: complete resection by radical lobectomy was achieved in 31 (94%) of them and 24 (73%) were pathological stage I. No perioperative death (within 31 days or related to surgery) were observed. After standard detection, the overall mortality was 1.9%, being related to resection volume (pneumonectomy 3.7% vs. lobectomy 1.7%) and extent of disese (stage I 1%, stage II 2.3%, stage III-IV 3.4%). In the early detection project, 6 subjects (0.4%) underwent a surgical biopsy for benign disease, without perioperative mortality. Conclusions: Early lung cancer resection has a favorable effect on surgical mortality, by preventing the need of pneumonectomy and reducing mortality after lobectomy. Annual spiral CT +- PET is a safe approach to early detection, with low frequency of invasive diagnostic procedures and absence of screening-related mortality. No significant financial relationships to disclose.
Abstract P344: Fibrosis-Related Biomarkers and the Risk of Incident Cardiovascular Disease: The Cardiovascular Health Study
Authors: Isha Agarwal, Nicole Glazer, Eddy Barasch, Mary Lou Biggs, Luc Djousse, John Gottdiener, Joachim Ix, Jorge Kizer, Eric Rimm, David Siscovick, Russell Tracy, Susan Zieman, Kenneth Mukamal
Journal: Circulation (2014)

Background: Fibrotic changes in the heart and vasculature have been implicated in a diverse range of cardiovascular disease (CVD). However, limited epidemiological data exists to support such associations. Methods: We determined prospective associations of two complementary biomarkers of fibrosis, transforming growth factor- β (TGF-β, n=1,371) and procollagen type III N-terminal propeptide (PIIINP, n=2,568), with congestive heart failure (CHF), myocardial infarction (MI), and stroke among community-living older adults in the Cardiovascular Health Study over 14 years of follow-up. Due to potentially pleiotropic effects of TGF-β on inflammation and fibrosis, we investigated effect modification by C-reactive protein (CRP) in secondary analyses. Results: In age, sex, race, and site-adjusted models, higher PIIINP was associated with risk of total CVD, CHF, and stroke, as was the combined measure of TGF-β and PIIINP (sum of z-scores). Most of these associations remained statistically significant in fully-adjusted models (Table). TGF-β was not associated with CVD in the full cohort, but associations with total CVD, CHF, and stroke were statistically significant among individuals with CRP above the median (2.3 mg/L) ( P -interaction=0.05). Associations involving PIIINP were also statistically significant and stronger among individuals with higher CRP. In the high CRP stratum, HRs for total CVD were 1.15 (CI: 1.02, 1.30) per SD TGF-β, 1.14 (CI: 1.04, 1.25) per SD PIIINP, and 1.21 (CI: 1.06, 1.38) per SD of the combined measure. In the low CRP stratum, HRs were 0.96 (CI: 0.82, 1.12) per SD of TGF-β, 1.02 (CI: 0.92, 1.12) per SD PIIINP, and 1.04 (CI: 0.90, 1.20) per SD of the combined measure. Conclusion: Our findings provide further evidence that circulating biomarkers of fibrosis, measured late in life, are associated with CVD. Research on whether TGF-β has a stronger pro-fibrotic effect in the setting of increased inflammation is warranted.
Emergence of lamivudine-resistant hepatitis B virus during combination antiretroviral therapy that includes lamivudine for patients co-infected with HIV and hepatitis B virus in China: a 2-year pilot cohort study
Authors: Yang Han, Lijun Gu, Ting Zhu, Taisheng Li, Xiaojing Song, Ying Huang, Feifei Yang, Shuo Guan, Jing Xie, Takaomi Ishida
Journal: The Lancet (2015)
XELOX compared to FOLFOX4: Survival and response results from XELOX-1/ NO16966, a randomized phase III trial of first-line treatment for patients with metastatic colorectal cancer (MCRC)
Authors: J. Cassidy, S. Clarke, E. Diaz-Rubio, W. Scheithauer, A. Figer, R. Wong, S. Koski, M. Lichinitser, T. Yang, L. Saltz
Journal: Journal of Clinical Oncology (2007)

4030 Background: In a phase II study in untreated MCRC patients, XELOX (capecitabine + oxaliplatin) appeared to have similar efficacy compared with previously published FOLFOX4 data [1]. We therefore started a phase III 2-arm open-label non-inferiority study comparing XELOX with FOLFOX4. In 2003 the addition of bevacizumab (Bev) to irinotecan/5-FU/LV was shown to improve progression-free survival (PFS) and overall survival [2]. We then amended our trial to a 2x2 partially blinded study to assess the addition of Bev. Methods: Original 2-arm study: XELOX (oxaliplatin 130 mg/m 2 iv, capecitabine 1,000 mg/m 2 bid oral d1- 14, q3w) vs. FOLFOX4 (oxaliplatin, 5-FU, leucovorin as described previously) [3]. In August 2003, amended to 2x2 partially blinded study: by adding Bev 7.5 mg/kg iv q3w or placebo (Pla) to XELOX and Bev 5 mg/kg iv q2w or Pla to FOLFOX4. Results: The original 2-arm study recruited 634 pts; after transition to 2x2, an additional 1400 patients were recruited. We previously reported non-inferiority in terms of PFS of XELOX vs. FOLFOX4 for the whole study population [4]. With 404 events, the overall survival data from the original 2-arm study are mature and show a HR for XELOX vs. FOLFOX4 of 0.93 (97.5% CI, 0.74–1.16). The response rates by investigator and independent review for the whole study population are shown in the table . Conclusions: XELOX is non-inferior to FOLFOX4. Overall survival data for the whole 2034 patient study population will be presented at the meeting. *no response assessment. 1. Cassidy J et al. J Clin Oncol 2004;22:2084–91. 2. Hurwitz H et al. N Eng J Med 2004;350:2335–42 3. De Gramont A et al. J Clin Oncol 2000;18:2938–47. 4. Cassidy J et al. Ann Oncol 2006;17(Suppl. 9):LBA3. [Table: see text] [Table: see text]
Rabies in a Dog Imported from Egypt with a Falsified Rabies Vaccination Certificate — Virginia, 2015
Authors: Julie R. Sinclair, Ryan M. Wallace, Karen Gruszynski, Marilyn Bibbs Freeman, Colin Campbell, Shereen Semple, Kristin Innes, Sally Slavinski, Gabriel Palumbo, Heather Bair-Brake, Lillian Orciari, Rene E. Condori, Adam Langer, Darin S. Carroll, Julia Murphy
Journal: MMWR Morbidity and Mortality Weekly Report (2015)

WHO Expert Consultation on RabiesAlthough there is debate about the estimated health burden of rabies, the estimates of direct mortality and the DALYs due to rabies are among the highest of the neglected tropical diseases.Poor surveillance, underreporting in many developing countries, frequent misdiagnosis of rabies, and an absence of coordination among all the sectors involved are likely to lead to underestimation of the scale of the disease.It is clear, however, that rabies disproportionately affects poor rural communities, and particularly children.Most of the expenditure for postexposure prophylaxis is borne by those who can least afford it.As a result of growing dog and human populations, the burden of human deaths from rabies and the economic costs will continue to escalate in the absence of concerted efforts and investment for control.Since the first WHO Expert Consultation on Rabies in 2004, WHO and its network of collaborating centres on rabies, specialized national institutions, members of the WHO Expert Advisory Panel on Rabies and partners such as the Gates Foundation, the Global Alliance for Rabies Control and the Partnership for Rabies Prevention, have been advocating the feasibility of rabies elimination regionally and globally and promoting research into sustainable cost-effective strategies.Those joint efforts have begun to break the cycle of rabies neglect, and rabies is becoming recognized as a priority for investment.This Consultation concluded that human dog-transmitted rabies is readily amenable to control, regional elimination in the medium term and even global elimination in the long term.A resolution on major neglected tropical diseases, including rabies, prepared for submission to the World Health Assembly in May 2013 aims at securing Member States' commitment to the control, elimination or eradication of these diseases.Endorsement of the resolution would open the door for exciting advances in rabies prevention and control.