tbuckley/cabot-search huggingface dataset:
A phase II trial of the PARP inhibitor veliparib (ABT888) and temozolomide for metastatic breast cancer.
Authors: S. J. Isakoff, B. Overmoyer, N. M. Tung, R. S. Gelman, V. L. Giranda, K. M. Bernhard, K. R. Habin, L. W. Ellisen, E. P. Winer, P. E. Goss
Journal: Journal of Clinical Oncology (2010)

1019 Background: Veliparib (ABT-888) is a novel oral inhibitor of Poly (ADP-Ribose) Polymerase (PARP) 1 and 2. Veliparib and temozolomide (TMZ) are synergistic in breast cancer xenograft models. TMZ has minimal activity in breast cancer likely due to robust repair methylated DNA adducts by the base excision repair (BER) pathway and MGMT. We hypothesized that combining veliparib with TMZ would be active in metastatic breast cancer (MBC). Methods: We conducted a single arm phase II trial of veliparib and TMZ in 41 MBC patients (pts). Eligibility included measurable MBC, >1 prior MBC therapy, and PS ≤ 2; previously treated stable brain metastases were allowed. Available archived tumor samples were collected. The initial Simon 2 stage design was modified to a single stage (n=41) due to rapid accrual. Patients received veliparib (40 mg PO BID days 1-7) and TMZ (150mg/m2 PO QD days 1-5) on a 28 day cycle. After higher than expected grade 4 thrombocytopenia was observed, the dose of veliparib was reduced to 30 mg BID. RECIST response was evaluated every 2 cycles. The primary endpoint was overall response rate. Secondary endpoints included PFS, OS, safety, and toxicity. Results: Between November 4, 2009 and December 28, 2009, 41 eligible pts (median age 51; range 32-67) were enrolled. At abstract submission, baseline characteristics for 35 evaluable pts include: median PS=0 (range 0-2); triple-negative (n=15), HER2+(n=5), and ER+/HER2- (n=15) subtypes; prior CNS disease (n=4). Toxicities: the most common grade 3/4 toxicities included thrombocytopenia (3 grade 3, 4 grade 4), and neutropenia (2 grade 3, 2 grade 4). Best response for 24 patients evaluable at the time of abstract submission includes 1 CR, 2 PR, 7 SD (all unconfirmed), and 14 PD; 17 pts are not yet evaluable for response. Conclusions: Combined veliparib and TMZ is active in MBC. Exploratory correlative studies including BRCA mutation analysis are underway to determine predictors of response. The dose and schedule of veliparib suggest the clinical activity seen is not likely due to veliparib alone but rather to the combination. Veliparib and TMZ may be a promising new strategy in MBC. The trial is fully accrued and final efficacy results will be presented. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Abbott Laboratories Abbott Laboratories Abbott Laboratories Abbott Laboratories
Determinants of relapse and survival in completely ressected non small cell lung cancer
Authors: Filipa Soares Pires, Gabriela Fernandes, Ana Paula Vaz, António Morais, Conceição Souto Moura, Pedro Bastos, Venceslau Hespanhol
Journal: European Respiratory Journal (2012)

INTRODUCTION: Lung ressection is the treatment of choice in Non-Small Cell Lung Cancer (NSCLC). Besides TNM staging, other features have been reported as significant prognostic factors.  AIM: To analyze factors affecting relapse and survival in NSCLC after complete ressection.  METHODS: A retrospective study was conducted, including patients with NSCLC completely ressected in the last 12 years. Clinical and histological factors were assessed and its influence on survival free of relapse and overall survival was determined.  RESULTS: 160 patients were included, 77.5% male and 22.5% female, with a median age of 65years. Relapse occurred in 69 patients (median survival free of relapse - 56 months). At univariate analysis, an association was found between reduced survival free of relapse and age≤62 years, clinical tumor size≥4cm, clinical TNM stage>IB, clinical T>1, clinical N>0, pathological TNM stage>IB, pathological T>2, pathological N>0 and vascular invasion. At multivariate analysis, tumor size≥4cm (p=0.004), pathological TNM stage>IB (p=0.023) and vascular invasion (p=0.024) were associated to a reduced survival free of relapse.  64 patients died (median overall survival – 112 months). At univariate analysis, an association was found between reduced overall survival and age≤62 years, clinical tumor size≥4cm, clinical TNM stage>IB, clinical N>0, pathological TNM stage>IB, pathological T>2, pathological N>0, vascular invasion and poor differentiation of tumor. At multivariate analysis, only pathological TNM stage>IB (p=0.029) remained associated a poorer overall survival.  CONCLUSION: Besides TNM staging, other features are important on relapse and survival and should be considered for adjuvant therapy.
Home-based rehabilitation program for lung cancer patients
Authors: Valérie Coats, François Maltais, Sébastien Simard, Έric Fréchette, Didier Saey
Journal: European Respiratory Journal (2011)

Patients with lung cancer often experience a reduction in exercise tolerance and muscle weakness. Despite the well-recognized effectiveness of pulmonary rehabilitation, few researches have studied its impact in lung cancer patients, particularly among whose awaiting for a lung resection surgery (LRS).   Objectives:  To investigate the feasibility of a short home-based rehabilitation program (HBRP) in patients with lung cancer awaiting for a LRS and to determine its effectiveness on exercise tolerance and skeletal muscle strength.   Methods:  Ten patients with lung cancer awaiting for a LRS were invited to a 4-week HBRP including moderate intensity aerobic activities (walking and cycling) and muscular training performed three times weekly. Prior to and after the 4-week HBRP, cardiopulmonary exercise test, six-minute walking test (6MWT) and muscle strengh were measured. Patients were asked to complete a diary including adverse events and training information.   Results:  No adverse event was reported during the rehabilitation program and 7 patients completed ≥75% of the HBRP. In the latter, the cycle endurance test duration (277±70 Vs 379±165s,p=0.08) and the 6MWT (597±49 Vs 624±39m, p   Conclusion:  In patients with lung cancer awaiting for LRS, home-based rehabilitation was feasible and induced some physiological gains, such as improved exercise tolerance and muscle strength. This may be clinically relevant, because poor exercise capacity is a strong predictor of postoperative complications in this population.  Project supported by the Canadian Lung Association.
Companion Animals and Human Health: An Overview
Authors: Andrew T B Edney
Journal: Journal of the Royal Society of Medicine (1995)

Domestic animals share our environment in a variety of ways. One of these ways is as companions in and around our homes. Although a wide variety of species are kept in households for this purpose, the great majority are dogs and cats. Sharing our environment with such animals has a profound effect on the health of the humans concerned. As keeping companion animals is a very widespread activity, about 50% of all households in the Western world have some sort of animal, the effects are far reaching.
Impact of reinforced education by telephone and short message service on the quality of bowel preparation: a randomized controlled study
Authors: Yoo Lee, Eun Kim, Jae Choi, Kyung Lee, Kyung Park, Kwang Cho, Byoung Jang, Woo Chung, Jae Hwang
Journal: Endoscopy (2015)

<b>Background and study aims:</b> High quality bowel preparation is essential for successful colonoscopy. This study aimed to assess the impact of reinforced education by telephone or short message service (SMS) on the quality of bowel preparation. <b>Patients and methods: </b>A prospective, endoscopist-blinded, randomized, controlled study was conducted. Reinforced education groups received additional education via reminders by telephone or SMS 2 days before colonoscopy. The primary outcome was the quality of the bowel preparation according to the Boston Bowel Preparation Scale (BBPS). The secondary outcomes included polyp detection rate (PDR), adenoma detection rate (ADR), tolerance, and subjective feelings of patients. <b>Results:</b> A total of 390 patients were included. Total BBPS score was significantly higher in the reinforced education groups than in the control group (mean [SD] telephone vs. control: 7.1 [1.2] vs. 6.3 [1.4],<i> P</i> < 0.001; SMS vs. control: 6.8 [1.3] vs. 6.3 [1.4], <i>P</i> = 0.027). Between the two interventions, there was no significant difference in total BBPS score. PDR and ADR were not different among groups. Reinforced education groups showed lower anxiety and better tolerance compared with controls. A preparation-to-colonoscopy time of > 6 hours and < 80 % of the purgative ingested were independent factors associated with inadequate bowel preparation (BBPS < 5), whereas re-education by telephone was inversely related to inadequate bowel preparation. <b>Conclusion: </b>SMS was the optimal education modality, and was as effective as telephone reminders for the quality of bowel preparation. A reinforced educational approach via telephone or SMS should be individualized, depending on the resource availability of each clinical practice. Trial registration: ClinicalTrials.gov (NCT01911052).
Drug combination that corrects deficient protein in cystic fibrosis improves lung function
Authors: S. Mayor
Journal: BMJ (2015)

A combination of two drugs used to correct levels of the transmembrane protein that is defective or deficient in cystic fibrosis significantly improves patients’ lung function, show the results of two randomised studies published in the New England Journal of Medicine .1

The studies included a total of 1108 patients with cystic fibrosis who were homozygous for the commonest mutation in the gene coding for cystic fibrosis transmembrane conductance regulator (CFTR) protein, Phe508del. They were randomised to lumacaftor, which corrects cellular misprocessing …
Dose-Intensive Epirubicin-Based Chemotherapy Is Superior to an Intensive Intravenous Cyclophosphamide, Methotrexate, and Fluorouracil Regimen in Metastatic Breast Cancer: A Randomized Multinational Study
Authors: Stephen P. Ackland, Antonio Anton, George Peter Breitbach, Elena Colajori, Jennifer M. Tursi, Carlos Delfino, Anna Efremidis, Adnan Ezzat, Alberto Fittipaldo, Kristo Kolaric, Massimo Lopez, Donatella Viaro
Journal: Journal of Clinical Oncology (2001)

PURPOSE: To determine the relative efficacy of a cyclophosphamide epirubicin and fluorouracil (CEF) regimen compared with an intravenous (IV) cyclophosphamide, methotrexate, and fluorouracil (CMF) combination in metastatic breast cancer. PATIENTS AND METHODS: Patients were randomized to receive either CEF (cyclophosphamide 400 mg/m 2 IV, epirubicin 50 mg/m 2 IV, and fluorouracil 500 mg/m 2 IV on days 1 and 8), or CMF (cyclophosphamide 500 mg/m 2 IV, methotrexate 40 mg/m 2 IV, and fluorouracil 600 mg/m 2 IV on days 1 and 8). Treatment was given in 3- to 4-week cycles for a total of six to nine cycles. RESULTS: A total of 460 patients (223 CEF and 237 CMF) were randomized. Overall response rate was superior for CEF than CMF in all randomized patients (57% v 46%, respectively; P = .01) and in the assessable subset (66% v 52%, respectively; P = .005). With a median follow-up of more than 20 months, time to progression (TTP) was significantly longer with CEF than CMF (median 8.9 v 6.3 months, respectively; P = .0064), as was time to treatment failure (TTF) (median 6.2 v 5.0 months, respectively; P = .01). Significant survival differences were not observed between CEF and CMF (median 20.1 v 18.2 months, respectively; P = .23). Granulocytopenia and infections were similar in both arms. Grade 3/4 nausea/vomiting and alopecia were more frequent with CEF, whereas diarrhea was more frequent with CMF. Cardiac toxicity, primarily asymptomatic, required withdrawal from study of 15 patients on CEF (7%) and one patient on CMF. CONCLUSION: This CEF regimen safely provides significantly better tumor control than CMF, manifest as a higher response rate, and longer TTP and TTF, but not survival, when used as first-line chemotherapy for metastatic breast cancer.
Methotrexate/fluorouracil scheduling influences normal tissue toxicity but not antitumor effects in patients with squamous cell head and neck cancer: results from a randomized trial.
Authors: G P Browman, M N Levine, M D Goodyear, R Russell, S D Archibald, B S Jackson, J E Young, V Basrur, C Johanson
Journal: Journal of Clinical Oncology (1988)

To test the hypothesis that sequential scheduling of methotrexate (MTX) and fluorouracil (FU) produces a synergistic antitumor effect, we randomized 113 patients with recurrent or locally advanced squamous cell carcinoma of the head and neck to receive MTX-FU either 18 hours apart or simultaneously, with leucovorin rescue. There were 100 patients with locally advanced newly presenting disease and 13 patients with recurrence. Excessive toxicity was observed in the first 11 patients who received MTX 250 mg/m2 administered intravenously (IV) and leucovorin at 36 hours, therefore all subsequent patients received MTX 200 mg/m2 administered IV and leucovorin at 24 hours. FU 600 mg/m2 IV was administered to all patients, and treatment was given on days 1 and 8 of 21-day cycles. The treatment groups were well balanced for known prognostic variables. The response rate was 47.3% (26 of 55) for simultaneous v 44.8% (26 of 58) for sequential therapy. These results exclude a 20% difference in response rate favoring sequential therapy at P = .04. There was no observed difference in survival between the two treatment arms (P = .55) with a minimum follow-up of 8 months. Toxicity was greater in patients who received sequential therapy, and the difference was confined to the gastrointestinal (GI) tract. A comparison of the distribution in maximum Eastern Cooperative Oncology Group (ECOG) toxicity scores during chemotherapy for the two treatment groups showed greater stomatitis (P = .001), diarrhea (P = .04), and overall toxicity (P = .02) for sequential treatment without an observed difference in bone marrow toxicity. The results of this trial indicate that sequential MTX-FU is not superior to simultaneous therapy for the treatment of patients with head and neck cancer. Biochemical modulation of MTX-FU by drug scheduling may occur in vivo and may be organ specific.
Cisplatin, etoposide, and ifosfamide salvage therapy for refractory or relapsing germ cell carcinoma.
Authors: A Harstrick, H J Schmoll, H Wilke, C H Köhne-Wömpner, M Stahl, C Schöber, J Casper, L Bruderek, E Schmoll, C Bokemeyer
Journal: Journal of Clinical Oncology (1991)

Thirty patients with metastatic progressive germ cell carcinoma who failed to be cured with first-line cisplatin chemotherapy were treated with a salvage regimen consisting of cisplatin 20 mg/m2, etoposide 100 mg/m2, and ifosfamide 1.2 g/m2 (PEI) intravenously (IV), days 1 to 5 every 3 weeks. Ten patients (33%) were tumor-free at the end of therapy. Complete response (CR) was achieved with chemotherapy alone in four patients and with additional surgery in six patients (two necroses, two mature teratomas, two carcinomas). Six patients (20%) had normalization of tumor markers but unresectable residual disease (Rm-), and the remaining 14 patients (46%) failed to respond. Of 10 patients with CR, nine (90%) relapsed again (eight carcinomas, one mature teratoma). The median duration of CR was 3.5 months. The median survival of the whole group was 311 days (range, 110 to 996+). Currently, seven of 30 patients are alive, and five of them are without signs of progressive tumor. The response to prior cisplatin therapy predicted for response and survival after PEI salvage therapy. Of 14 patients with prior CR, eight (57%) achieved a second CR compared with one of 11 (9%) with prior unfavorable response (P = .039). The median survival for patients with prior favorable response was 400 days, compared with 251 days for patients with prior unfavorable response (P less than .001). Myelosuppression was dose-limiting, with leukopenia greater than grade 2 in 84% and thrombocytopenia greater than grade 2 in 51% of all cycles. This three-drug regimen can induce a second CR in one third of patients with relapsed or refractory germ cell carcinoma. Only those patients with prior favorable responses can expect to be cured by this salvage regimen, while patients with prior unfavorable response should be considered for alternative salvage approaches.
Three-Dimensional Analysis With MRI and PET of the Size, Shape, and Function of the Thalamus in the Schizophrenia Spectrum
Authors: Erin A. Hazlett, Monte S. Buchsbaum, William Byne, Tse-Chung Wei, Jacqueline Spiegel-Cohen, Craig Geneve, Rayzel Kinderlehrer, M. Mehmet Haznedar, Lina Shihabuddin, Larry J. Siever
Journal: American Journal of Psychiatry (1999)

In an exploration of the schizophrenia spectrum, the authors compared thalamic size, shape, and metabolic activity in unmedicated patients with schizophrenia and schizotypal personality disorder to findings in age- and sex-matched healthy control subjects.Coregistered magnetic resonance imaging (MRI) and positron emission tomography scans were obtained in 27 schizophrenic patients, 13 patients with schizotypal personality disorder, and 32 control subjects who performed a serial verbal learning test during tracer uptake. After thalamus edges were outlined on 1.2-mm MRI scans, a radial warping program yielded significance probability mapping in three dimensions.Significance probability mapping (with resampling) identified an area in the region of the mediodorsal nucleus bilaterally with significantly lower relative metabolism in the schizophrenia group than in either the control or schizotypal personality disorder groups, which did not differ from each other. The three groups did not differ significantly in total thalamic volume in square millimeters or thalamic volume relative to brain volume. Shape analyses revealed that schizophrenic patients had significantly fewer pixels in the left anterior region, whereas patients with schizotypal personality disorder had significantly fewer pixels in the region of the right mediodorsal nucleus than did control subjects.Schizophrenic patients showed significant metabolism and shape differences from control subjects in selective subregions of the thalamus, whereas patients with schizotypal personality disorder showed only a difference in shape. Because the mediodorsal and anterior nuclei have different connections with limbic and prefrontal structures, the anterior thalamic shrinkage and mediodorsal metabolic and shape changes might relate to the different clinical pictures in schizotypal personality disorder and schizophrenia.
Neuropeptides and the Integration of Motor Responses to Dehydration
Authors: Alan G. Watts
Journal: Annual Review of Neuroscience (2001)

Drinking and eating are critically important motivated behaviors whose expression is usually tightly linked; under conditions of spontaneous intake, disruption of one usually disturbs the other. This characteristic is exemplified by dehydration-induced anorexia in which increasing plasma osmolality leads to a centrally generated reduction in food intake, which is then rapidly reversed as water is again made available. This review discusses, at a systems level, how the brain is organized to generate these behaviors and how dehydration affects the expression of neuropeptides in sets of anatomically defined forebrain circuits that contribute to the integration of motor outputs. These findings are then used to consider how altered neuropeptidergic signaling operates within motor drive networks and how these changes may impact the way neuroendocrine, autonomic, and behavioral motor systems respond to this fundamental homeostatic challenge.
Cyclophosphamide, methotrexate, and fluorouracil with and without doxorubicin in the adjuvant treatment of resectable breast cancer with one to three positive axillary nodes.
Authors: A Moliterni, G Bonadonna, P Valagussa, L Ferrari, M Zambetti
Journal: Journal of Clinical Oncology (1991)

In the attempt to improve current adjuvant results in patients with one to three positive axillary lymph nodes, in November 1981 we activated a prospective randomized study to assess the effectiveness of intravenous (IV) cyclophosphamide, methotrexate, and fluorouracil (CMF) for 12 courses versus CMF for eight courses followed by Adriamycin (doxorubicin; Farmitalia Carlo Erba, Milan, Italy) for four courses. The 5-year results were evaluated in a total of 486 patients entered into the study up to December 1987. CMF chemotherapy was delivered IV for a total of 12 courses when given alone and for eight courses when followed by four courses of Adriamycin. All drugs were recycled every 3 weeks. Rather than temporarily reducing doses, drug administration was delayed for 1 to 2 weeks in the face of myelosuppression on the planned day of treatment. After a median follow-up of 61 months, no significant differences were evident between the treatment groups in terms of relapse-free (CMF 74% v CMF followed by Adriamycin 72%) and total survival (CMF 89% v CMF followed by Adriamycin 86%). Drug treatments were fairly well tolerated and devoid of life-threatening toxicity. Present results, which were not influenced by menopausal status, indicate that Adriamycin given after CMF failed to improve treatment outcome over CMF alone. However, the role of Adriamycin in an adjuvant setting remains to be further clarified. Considering the good 5-year results achieved in this study at the expense of minimal toxicity, full-dose CMF remains, at present, the adjuvant chemotherapy of choice for patients with one to three positive nodes.
Palatability Can Drive Feeding Independent of AgRP Neurons
Authors: Raphaël G.P. Denis, Aurélie Joly-Amado, Emily Webber, Fanny Langlet, Marie Schaeffer, Stéphanie L. Padilla, Céline Cansell, Bénédicte Dehouck, Julien Castel, Anne-Sophie Delbès, Sarah Martinez, Amélie Lacombe, Claude Rouch, Nadim Kassis, Jean-Alain Fehrentz, Jean Martinez, Pascal Verdié, Thomas S. Hnasko, Richard D. Palmiter, Michael J. Krashes, Ali D. Güler, Christophe Magnan, Serge Luquet
Journal: Cell Metabolism (2015)
Pirfenidone treatment in idiopathic pulmonary fibrosis: An Italian case series
Authors: Claudia Ravaglia, Carlo Gurioli, Micaela Romagnoli, GianLuca Casoni, Sara Tomassetti, Christian Gurioli, Venerino Poletti
Journal: European Respiratory Journal (2013)

Background and objective : Idiopathic pulmonary fibrosis (IPF) is a progressive fibrotic interstitial lung disease with an estimated median survival of only 2-3 years from initial diagnosis. To date, Pirfenidone is the only pharmacological agent that has been approved in the European Union for the treatment of IPF. We report our experience on efficacy of pirfenidone in IPF in our centre.   Patients and methods : we studied all the patients with a diagnosis of IPF who have been treated with Pirfenidone over the period from September 2008 to February 2013 in our centre; follow-up time was calculated from the starting point of pirfenidone to the last patient visit or to the interruption of the drug.   Results  :  81 patients with IPF were treated with pirfenidone but only 68 were included in the study as 13 patients had discontinued the drug in the first thrre months of treatment because of side effects. Mean follow-up time was 43,48 weeks [range 12 - 219], mean age was 69 years [range 41 - 81], 58 were male (85%) and 10 were female (15%). Mean FVC at the starting point of pirfenidone was 70,75% and DLCO was 42,82%. At the end of the follow-up period mean FVC was 69,26% and DLCO was 41,39%; 40 patients (58,8 %) were stable or have significantly improved after treatment while 20 patients (29,4 %) have significantly worsened after treatment. Patients who got worse were all smokers but 2 (90%).   Conclusion : Pirfenidone was generally well tolerated and the course of the disease was stable during treatment with pirfenidone in the majority of patients. Our results are in line with the previous published safety and efficacy data on pirfenidone as treatment for IPF.