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  1. Modified Synthesis of Erlotinib Hydrochloride

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    Leila Barghi

    2012-06-01

    Full Text Available Purpose: An improved and economical method has been described for the synthesis of erlotinib hydrochloride, as a useful drug in treatment of non-small-cell lung cancer. Methods: Erlotinib hydrochloride was synthesized in seven steps starting from 3, 4-dihydroxy benzoic acid. In this study, we were able to modify one of the key steps which involved the reduction of the 6-nitrobenzoic acid derivative to 6-aminobenzoic acid derivative. An inexpensive reagent such as ammonium formate was used as an in situ hydrogen donor in the presence of palladium/charcoal (Pd/C instead of hydrogen gas at high pressure. Results: This proposed method proceeded with 92% yield at room temperature. Synthesis of erlotinib was completed in 7 steps with overall yield of 44%.Conclusion: From the results obtained it can be concluded that the modified method eliminated the potential danger associated with the use of hydrogen gas in the presence of flammable catalysts. It should be mentioned that the catalyst was recovered after the reaction and could be used again.

  2. [11C] labeled erlotinib as a new radiotracer for identification of patients responding to erlotinib treatment

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    Memon, Ashfaque Ahmed; Weber, Britta; Jakobsen, Steen

    2009-01-01

    Erlotinib (Tarceva®) is a tailored drug targeting the Epidermal Growth Factor Receptor (EGFR), which is commonly overexpressed in various human cancers including lung cancer. The purpose of this study was to develop a method for identification of lung cancer patients that respond to erlotinib...... the accumulation of [11C] erlotinib was higher in the tumor than in all other organs except the liverwhich is the main organ of erlotinib metabolism (Cancer Research, 2009 69: 873-878). We have now extended this study to patients with the aim to identify the subset of patients that will respond to Erlotinib...... treatment (10-15 %). Tumors were identified by routine CT scan and [18F]-2-fluoro- 2-deoxyglucose (FDG) PET/CT and compared with [11C] erlotinib PET/CT. As expected, all patients examined so far (n=4) showed [18F] FDG uptake. Our results with [11C] erlotinib show that tumors can be identified by [11C...

  3. Erlotinib

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    ... of medications called kinase inhibitors. It works by blocking the action of an abnormal protein that signals ... acne and may affect the skin on the face, upper chest, or back) blistering, peeling, dry, or ...

  4. Erlotinib and the Risk of Oral Cancer

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    William, William N.; Papadimitrakopoulou, Vassiliki; Lee, J. Jack; Mao, Li; Cohen, Ezra E.W.; Lin, Heather Y.; Gillenwater, Ann M.; Martin, Jack W.; Lingen, Mark W.; Boyle, Jay O.; Shin, Dong M.; Vigneswaran, Nadarajah; Shinn, Nancy; Heymach, John V.; Wistuba, Ignacio I.; Tang, Ximing; Kim, Edward S.; Saintigny, Pierre; Blair, Elizabeth A.; Meiller, Timothy; Gutkind, J. Silvio; Myers, Jeffrey; El-Naggar, Adel; Lippman, Scott M.

    2016-01-01

    IMPORTANCE Standard molecularly based strategies to predict and/or prevent oral cancer development in patients with oral premalignant lesions (OPLs) are lacking. OBJECTIVE To test if the epidermal growth factor receptor inhibitor erlotinib would reduce oral cancer development in patients with high-risk OPLs defined by specific loss of heterozygosity (LOH) profiles. Secondary objectives included prospective determination of LOH as a prognostic marker in OPLs. DESIGN The Erlotinib Prevention of Oral Cancer (EPOC) study was a randomized, placebo-controlled, double-bind trial. Accrual occurred from November 2006 through July 2012, with a median follow-up time of 35 months in an ambulatory care setting in 5 US academic referral institutions. Patients with OPLs were enrolled in the protocol, and each underwent LOH profiling (N = 379); they were classified as high-risk (LOH-positive) or low-risk (LOH-negative) patients based on their LOH profiles and oral cancer history. The randomized sample consisted of 150 LOH-positive patients. INTERVENTIONS Oral erlotinib treatment (150mg/d) or placebo for 12 months. MAIN OUTCOMES AND MEASURES Oral cancer–free survival (CFS). RESULTS A total of 395 participants were classified with LOH profiles, and 254 were classified LOH positive. Of these, 150 (59%) were randomized, 75 each to the placebo and erlotinib groups. The 3-year CFS rates in placebo- and erlotinib-treated patients were 74%and 70%, respectively (hazard ratio [HR], 1.27; 95%CI, 0.68–2.38; P = .45). The 3-year CFS was significantly lower for LOH-positive compared with LOH-negative groups (74%vs 87%, HR, 2.19; 95%CI, 1.25–3.83; P = .01). Increased EGFR gene copy number correlated with LOH-positive status (P < .001) and lower CFS (P = .01). The EGFR gene copy number was not predictive of erlotinib efficacy. Erlotinib-induced skin rash was associated with improved CFS (P = .01). CONCLUSIONS AND RELEVANCE In this trial, LOH was validated as a marker of oral cancer risk and

  5. Erlotinib induced target-like purpura.

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    Rungtrakulchai, R; Rerknimitr, P

    2014-02-18

    Erlotinib is an epidermal growth factor receptor (EGFR) inhibitor, used as a treatment for advanced stage cancer. The most common side effect is cutaneous toxicity including the already known papulopustular reaction. We herein report a case of erlotinib induced target-like purpura, a peculiar cutaneous adverse event. A 57-year-old patient with advanced non-small cell lung cancer was treated by erolotinib 150 mg daily. After taking the drug for three days, an unusual target-like purpura developed on her lower legs. Skin biopsy specimen taken from the lesion revealed an extravasation of erythrocytes in the upper dermis without destruction of blood vessel walls. This skin eruption cleared after the drug was withdrawn and recurred after erlotinib was re-challenged. The mechanism underlying this cutaneous adverse event remains to be elucidated. Physicians should be aware of the rare side effect of this increasingly used drug.

  6. Nanoparticulation improves bioavailability of Erlotinib.

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    Yang, Kyung Mi; Shin, In Chul; Park, Joo Won; Kim, Kab-Sig; Kim, Dae Kyong; Park, Kyungmoon; Kim, Kunhong

    2017-09-01

    Nanoparticulation using fat and supercritical fluid (NUFS TM ) is a drug delivery platform technology enabling efficient and effective formulation of poorly soluble drugs. We performed experiments to examine whether NUFS™ could improve poor bioavailability and reduce fed-fasted bioavailability variances of erlotinib (Ert). NUFS-Ert was prepared using NUFS™ technology; its physical properties were characterized, and drug release was measured. Furthermore, in vitro and in vivo efficacy tests and pharmacokinetic analysis were performed. NUFS-Ert nanoparticles had an average size of 250 nm and were stable for 2 months at 40 °C, 4 °C, and room temperature. The dissolution rate of NUFS-Ert increased in bio-relevant dissolution media. NUFS-Ert was more potent in inhibiting EGF signaling and in suppressing the proliferation of A549, a human non-small cell lung cancer cell line. Furthermore, A549 xenografts in BALB/c nude mice treated with NUFS-Ert regressed more efficiently than those in the mice treated with vehicle or Tarceva ® . In addition, experimental lung metastasis was more efficiently inhibited by NUFS-Ert than by Tarceva ® . The relative bioavailability of NUFS-Ert compared with that of Tarceva ® was 550% and the ratio of the area under the concentration-time curve (AUC) of fed state to the AUC of fasted state was 1.8 for NUFS-Ert and 5.8 for Tarceva ® . NUFS-Ert could improve poor bioavailability and reduce fed-fasted bioavailability variances of Ert. NUFS-Ert was more efficacious than Tarceva ® .

  7. Erlotinib-induced rash spares previously irradiated skin

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    Lips, Irene M.; Vonk, Ernest J.A.; Koster, Mariska E.Y.; Houwing, Ronald H.

    2011-01-01

    Erlotinib is an epidermal growth factor receptor inhibitor prescribed to patients with locally advanced or metastasized non-small cell lung carcinoma after failure of at least one earlier chemotherapy treatment. Approximately 75% of the patients treated with erlotinib develop acneiform skin rashes. A patient treated with erlotinib 3 months after finishing concomitant treatment with chemotherapy and radiotherapy for non-small cell lung cancer is presented. Unexpectedly, the part of the skin that had been included in his previously radiotherapy field was completely spared from the erlotinib-induced acneiform skin rash. The exact mechanism of erlotinib-induced rash sparing in previously irradiated skin is unclear. The underlying mechanism of this phenomenon needs to be explored further, because the number of patients being treated with a combination of both therapeutic modalities is increasing. The therapeutic effect of erlotinib in the area of the previously irradiated lesion should be assessed. (orig.)

  8. Combination erlotinib-cisplatin and Atg3-mediated autophagy in erlotinib resistant lung cancer.

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    Jasmine G Lee

    Full Text Available Tyrosine kinase inhibitors such as erlotinib are commonly used as a therapeutic agent against cancer due to its relatively low side-effect profile and, at times, greater efficacy. However, erlotinib resistance (ER in non-small cell lung cancer is being recognized as a major problem. Therefore, understanding the mechanism behind ER and developing effective regimens are needed. Autophagy's role in cancer has been controversial and remains unclear. In this study, we examined the effectiveness of low dose erlotinib-cisplatin combination in erlotinib resistant lung adenocarcinoma (ERPC9 cells and the role of autophagy in ER. ERPC9 cells were established from erlotinib sensitive PC9 cells. Appropriate treatments were done over two days and cell survival was quantified with Alamar Blue assay. LC3II and regulatory proteins of autophagy were measured by western blot. Small interfering RNA (siRNA was utilized to inhibit translation of the protein of interest. In ERPC9 cells, combination treatment induced synergistic cell death and a significant decrease in autophagy. At baseline, ERPC9 cells had a significantly higher LC3II and lower p-mTOR levels compared to PC9 cells. The addition of rapamycin increased resistance and 3-methyladenine sensitized ERPC9 cells, indicating autophagy may be acting as a protective mechanism. Further examination revealed that ERPC9 cells harbored high baseline Atg3 levels. The high basal Atg3 was targeted and significantly lowered with combination treatment. siRNA transfection of Atg3 resulted in the reversal of ER; 42.0% more cells died in erlotinib-alone treatment with transfection compared to non-transfected ERPC9 cells. We reveal a novel role for Atg3 in the promotion of ER as the inhibition of Atg3 translation was able to result in the re-sensitization of ERPC9 cells to erlotinib-alone treatment. Also, we demonstrate that combination erlotinib-cisplatin is an effective treatment against erlotinib resistant cancer by

  9. Erlotinib e metástases cerebrais

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    Fernando Barata

    2008-10-01

    Full Text Available Resumo: Relatamos dois casos de carcinoma pulmonar de não pequenas células (CPNPC com metástases cerebrais que após quimioterapia sistémica receberam em segunda e terceira linha erlotinib 150 mg/dia, oral, com resposta completa das lesões secundárias cerebrais e franca resposta parcial das lesões torácicas.A metastização cerebral, bastante prevalente no contexto do CPNPC, está associada a escassas opções terapêuticas eficazes e, consequentemente, a uma sobre-vida mediana de 4 a 6 meses.Estes casos alertam para o erlotinib como uma excelente opção terapêutica para estes doentes. Os autores propõem um ensaio clínico com este fármaco neste grupo de doentes, procurando determinar da resposta objectiva.Rev Port Pneumol 2008; XIV (Supl 3: S35-S42 Abstract: We report two cases of brain metastases in context of non small cell lung cancer (NSCLC. After having progressed to chemotherapy they received erlotinib 150 mg/m2 orally daily, with complete response of brain metastasis and partial response of thoracic lesions.Brain metastases are both prevalent and a major cause of mortality in NSCLC, with few systemic treatment options. Median survival after whole brain radiotherapy is 4-6 months and the role of systemic therapy for brain metastases is limited with the most drugs use to stage IV disease ineffective in this setting.This case demonstrates that brain metastases may be sensitive to erlotinib and give to us growing body of evidence that EGFR-associated tyrosine kinase inhibition is a feasible strategy in the management of NSCLC patients with brain metastasesWe propose further study into the continued use of this drug in the situation where there is a differential response.Rev Port Pneumol 2008; XIV (Supl 3: S35-S42 Palavras-chave: Erlotinib, metástase cerebral, cancro do pulmão, Key-words: Erlotinib, brain metastasis, lung cancer

  10. EGFR mutation frequency and effectiveness of erlotinib

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    Weber, Britta; Hager, Henrik; Sorensen, Boe S

    2014-01-01

    mutation (S768I), and two complex mutations. Seven percent of the patients were never smokers. The differences in median progression-free survival and overall survival between the mutated group and the wild-type group were 8.0 vs. 2.5 months, p...-1 vs. 2-3) and line of treatment (1st vs. 2nd and 3rd) had no influence on outcome in EGFR-mutated patients. CONCLUSION: We found a higher frequency of EGFR mutations than expected in a cohort with less than 10% never smokers. The outcome after treatment with erlotinib was much better in patients......OBJECTIVES: In 2008, we initiated a prospective study to explore the frequency and predictive value of epidermal growth factor receptor (EGFR) mutations in an unselected population of Danish patients with non-small cell lung cancer offered treatment with erlotinib, mainly in second-line. MATERIALS...

  11. Erlotinib in previously treated non-small-cell lung cancer

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    Smrdel, U.; Kovac, V.

    2006-01-01

    Background. Erlotinib is a novel biological anti-tumour agent in the treatment of advanced non small cell lung cancer. It represents the molecularly-targeted therapy which has been studied extensively. Case report. We present a case of a patient who suffered from advanced non-small-cell lung cancer. After the progress of disease following a prior chemotherapy he was treated with erlotinib with remarkable effect which was shown at chest x ray and symptoms were quite reduced. Conclusions. In selected patients with advanced non-small-cell lung cancer Erlotinib improves survival and symptom control as it results in presented case. (author)

  12. [Functional impairment and radiologic fasciitis under erlotinib therapy].

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    Osdoit, S; Wierzbicka, E; Guillet, G

    2011-01-01

    Targeted molecules are recent and valuable weapons in the management of certain cancers. Among them, erlotinib is an inhibitor of epidermal growth factor receptor approved in non-small lung cancer and pancreatic cancer after failure of first line treatment. Erlotinib is responsible for many cutaneous side effects. We report a case of acute symptomatic fasciitis that has occurred during erlotinib therapy. To our knowledge it is the first case described. A 56-year-old man was treated with erlotinib for a metastatic non-small lung adenocarcinoma. Shortly after the treatment by erlotinib was introduced, he had a severe acneiform rash resistant to doxycycline treatment. After a year of treatment, he presented intense pain in the legs with functional impairment. Medical imaging confirmed fasciitis. It regressed along with the rash after using strong topical corticosteroids during ten days. Besides bacterial fasciitis, inflammatory and oedematous fasciitis have varied aetiologies. The occurrence of a documented fasciitis during anti EGFR-therapy is original and raises the question of underlying mechanism. We suggest three pathophysiological mechanisms: spreading by contiguity; paraneoplastic fasciitis, or specific lesion of the fascia due to anti-EGFR. Copyright © 2011 Elsevier Masson SAS. All rights reserved.

  13. Pilot study of erlotinib in patients with acute myeloid leukemia.

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    Sayar, Hamid; Czader, Magdalena; Amin, Chirag; Cangany, Mary; Konig, Heiko; Cripe, Larry D

    2015-02-01

    We conducted a pilot study to investigate clinical efficacy of tyrosine kinase inhibitor erlotinib in the treatment of acute myeloid leukemia (AML). A total of 11 patients with de novo AML were treated, including 2 with relapsed and/or refractory disease and 9 older patients with previously untreated AML. Patients with high baseline leukocyte count were excluded. Erlotinib was given orally at 150 mg per day continuously in 28-day cycles. The treatment was tolerated well, and no toxicities were observed. An initial reduction in circulating blasts, followed by disease progression, was observed in 2 patients. Nine other patients did not demonstrate any response in blood or bone marrow. Baseline and post-cycle 1 flow-cytometry were performed on bone marrow blasts to investigate signs of differentiation. No immunophenotypic changes suggestive of differentiation were observed. This pilot study did not demonstrate response to standard doses of erlotinib in patients with AML. Copyright © 2014 Elsevier Ltd. All rights reserved.

  14. Erlotinib promotes endoplasmic reticulum stress-mediated injury in the intestinal epithelium

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    Fan, Lu; Hu, Lingna; Yang, Baofang; Fang, Xianying; Gao, Zhe; Li, Wanshuai; Sun, Yang; Shen, Yan; Wu, Xuefeng [State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, 22 Hankou Road, Nanjing 210093 (China); Shu, Yongqian [Department of Clinical Oncology, The First Affiliated Hospital of Nanjing Medical University, 140 Hanzhong Road, Nanjing 210029 (China); Gu, Yanhong, E-mail: guluer@163.com [Department of Clinical Oncology, The First Affiliated Hospital of Nanjing Medical University, 140 Hanzhong Road, Nanjing 210029 (China); Wu, Xudong, E-mail: xudongwu@nju.edu.cn [State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, 22 Hankou Road, Nanjing 210093 (China); Xu, Qiang, E-mail: molpharm@163.com [State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, 22 Hankou Road, Nanjing 210093 (China)

    2014-07-01

    Erlotinib, a popular drug for treating non-small cell lung cancer (NSCLC), causes diarrhea in approximately 55% of patients receiving this drug. In the present study, we found that erlotinib induced barrier dysfunction in rat small intestine epithelial cells (IEC-6) by increasing epithelial permeability and down-regulating E-cadherin. The mRNA levels of various pro-inflammatory cytokines (Il-6, Il-25 and Il-17f) were increased after erlotinib treatment in IEC-6 cells. Erlotinib concentration- and time-dependently induced apoptosis and endoplasmic reticulum (ER) stress in both IEC-6 and human colon epithelial cells (CCD 841 CoN). Intestinal epithelial injury was also observed in male C57BL/6J mice administrated with erlotinib. Knockdown of C/EBP homologous protein (CHOP) with small interference RNA partially reversed erlotinib-induced apoptosis, production of IL-6 and down-regulation of E-cadherin in cultured intestinal epithelial cells. In conclusion, erlotinib caused ER stress-mediated injury in the intestinal epithelium, contributing to its side effects of diarrhea in patients. - Highlights: • Erlotinib destroyed barrier integrity both in vitro and in vivo. • Erlotinib induced inflammation both in vitro and in vivo. • Erlotinib induced apoptosis both in vitro and in vivo. • ER stress contributed to erlotinib-induced barrier dysfunction.

  15. Erlotinib promotes endoplasmic reticulum stress-mediated injury in the intestinal epithelium

    International Nuclear Information System (INIS)

    Fan, Lu; Hu, Lingna; Yang, Baofang; Fang, Xianying; Gao, Zhe; Li, Wanshuai; Sun, Yang; Shen, Yan; Wu, Xuefeng; Shu, Yongqian; Gu, Yanhong; Wu, Xudong; Xu, Qiang

    2014-01-01

    Erlotinib, a popular drug for treating non-small cell lung cancer (NSCLC), causes diarrhea in approximately 55% of patients receiving this drug. In the present study, we found that erlotinib induced barrier dysfunction in rat small intestine epithelial cells (IEC-6) by increasing epithelial permeability and down-regulating E-cadherin. The mRNA levels of various pro-inflammatory cytokines (Il-6, Il-25 and Il-17f) were increased after erlotinib treatment in IEC-6 cells. Erlotinib concentration- and time-dependently induced apoptosis and endoplasmic reticulum (ER) stress in both IEC-6 and human colon epithelial cells (CCD 841 CoN). Intestinal epithelial injury was also observed in male C57BL/6J mice administrated with erlotinib. Knockdown of C/EBP homologous protein (CHOP) with small interference RNA partially reversed erlotinib-induced apoptosis, production of IL-6 and down-regulation of E-cadherin in cultured intestinal epithelial cells. In conclusion, erlotinib caused ER stress-mediated injury in the intestinal epithelium, contributing to its side effects of diarrhea in patients. - Highlights: • Erlotinib destroyed barrier integrity both in vitro and in vivo. • Erlotinib induced inflammation both in vitro and in vivo. • Erlotinib induced apoptosis both in vitro and in vivo. • ER stress contributed to erlotinib-induced barrier dysfunction

  16. The plasma and cerebrospinal fluid pharmacokinetics of erlotinib and its active metabolite (OSI-420) after intravenous administration of erlotinib in non-human primates.

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    Meany, Holly J; Fox, Elizabeth; McCully, Cynthia; Tucker, Chris; Balis, Frank M

    2008-08-01

    Erlotinib hydrochloride is a small molecule inhibitor of epidermal growth factor receptor (EGFR). EGFR is over-expressed in primary brain tumors and solid tumors that metastasize to the central nervous system. We evaluated the plasma and cerebrospinal fluid (CSF) pharmacokinetics of erlotinib and its active metabolite OSI-420 after an intravenous (IV) dose in a non-human primate model. Erlotinib was administered as a 1 h IV infusion to four adult rhesus monkeys. Serial blood and CSF samples were drawn over 48 h and erlotinib and OSI-420 were quantified with an HPLC/tandem mass spectroscopic assay. Pharmacokinetic parameters were estimated using non-compartmental and compartmental methods. CSF penetration was calculated from the AUC(CSF):AUC(plasma). Erlotinib disappearance from plasma after a short IV infusion was biexponential with a mean terminal half-life of 5.2 h and a mean clearance of 128 ml/min per m(2). OSI-420 exposure (AUC) in plasma was 30% (range 12-59%) of erlotinib, and OSI-420 clearance was more than 5-fold higher than erlotinib. Erlotinib and OSI-420 were detectable in CSF. The CSF penetration (AUC(CSF):AUC(plasma)) of erlotinib and OSI-420 was OSI-420 are measurable in CSF after an IV dose. The drug exposure (AUC) in the CSF is limited relative to total plasma concentrations but is substantial relative the free drug exposure in plasma.

  17. Effects of the EGFR Inhibitor Erlotinib on Magnesium Handling

    NARCIS (Netherlands)

    Dimke, Henrik; van der Wijst, Jenny; Alexander, Todd R.; Meijer, Inez M. J.; Mulder, Gemma M.; van Goor, Harry; Tejpar, Sabine; Hoenderop, Joost G.; Bindels, Rene J.

    A mutation in pro-EGF causes isolated hypomagnesemia, and monoclonal antibodies targeting the extracellular domain of the EGF receptor (EGFR) affect epithelial Mg2+ transport. The effect of the EGFR tyrosine kinase inhibitor erlotinib on Mg2+ homeostasis, however, remains unknown. Here, we injected

  18. Phase I Trial Using Induction Ciplatin, Docetaxel, 5-FU and Erlotinib Followed by Cisplatin, Bevacizumab and Erlotinib With Concurrent Radiotherapy for Advanced Head and Neck Cancer.

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    Ahn, Peter H; Machtay, Mitchell; Anne, Pramila R; Cognetti, David; Keane, William M; Wuthrick, Evan; Dicker, Adam P; Axelrod, Rita S

    2018-05-01

    Bevacizumab (avastin) and erlotinib (tarceva) had shown early clinical activity against head and neck cancer (HNC). We initiated a phase I trial of induction cisplatin, docetaxel, 5-fluorouracil and erlotinib (TPF-E) followed by cisplatin, bevacizumab and erlotinib (PA-E) with radiotherapy (XRT) for advanced HNC. The goal was to determine maximum tolerated erlotinib dose. Eligible patients had stage IVA or higher HNC with good performance status, hematologic, and renal reserve. Two cycles of induction TPF-E were administered. XRT was administered with concurrent weekly cisplatin and bevacizumab every 2 weeks. Initial erlotinib dose was 50 mg daily from start of induction chemotherapy until radiotherapy completion. Erlotinib dose escalations to 100 and 150 mg were planned. Thirteen patients with previously untreated locoregional disease (11 patients) or oligometastatic (2 patients) HNC were enrolled. Totally, 11 of 13 patients completed XRT as planned. Four of 8 patients in cohort 1 (erlotinib 50 mg), 3 of 4 patients in cohort 2 (100 mg), and 0 of 1 patients in cohort 3 (150 mg) completed the regimen. Two patients had significant gastrointestinal complications (bleeding and perforation), and 1 had dose-limiting diarrhea. Maximum tolerated dose was reached at 50 mg erlotinib. At median 23.4 months follow-up, 5 patients (38%) have no evidence of disease, and 2 (15%) have stable but measurable disease. Erlotinib in combination with induction TPF followed by erlotinib, cisplatin, and bevacizumab with XRT is active but toxic. Gastrointestinal toxicities partly caused high rates of study withdrawal. All doses studied in this protocol caused unexpected toxicities and we do not recommend advancement to phase II.

  19. Pharmacokinetic drug-drug interaction between erlotinib and paracetamol: A potential risk for clinical practice.

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    Karbownik, Agnieszka; Szałek, Edyta; Sobańska, Katarzyna; Grabowski, Tomasz; Wolc, Anna; Grześkowiak, Edmund

    2017-05-01

    Erlotinib is a tyrosine kinase inhibitor available for the treatment of non-small cell lung cancer. Paracetamol is an analgesic agent, commonly used in cancer patients. Because these drugs are often co-administered, there is an increasing issue of interaction between them. The aim of the study was to investigate the effect of paracetamol on the pharmacokinetic parameters of erlotinib, as well as the influence of erlotinib on the pharmacokinetics of paracetamol. The rabbits were divided into three groups: the rabbits receiving erlotinib (I ER ), the group receiving paracetamol (II PR ), and the rabbits receiving erlotinib+paracetamol (III ER+PR ). A single dose of erlotinib was administered orally (25mg) and was administered intravenously (35mg/kg). Plasma concentrations of erlotinib, its metabolite (OSI420), paracetamol and its metabolites - glucuronide and sulphate were measured with the validated method. During paracetamol co-administration we observed increased erlotinib maximum concentration (C max ) and area under the plasma concentration-time curve from time zero to infinity (AUC 0-∞ ) by 87.7% and 31.1%, respectively. In turn, erlotinib lead to decreased paracetamol AUC 0-∞ by 35.5% and C max by 18.9%. The mean values of paracetamol glucuronide/paracetamol ratios for C max were 32.2% higher, whereas paracetamol sulphate/paracetamol ratios for C max and AUC 0-∞ were 37.1% and 57.1% lower in the II PR group, when compared to the III ER+PR group. Paracetamol had significant effect on the enhanced plasma exposure of erlotinib. Additionally, erlotinib contributed to the lower concentrations of paracetamol. Decreased glucuronidation and increased sulphation of paracetamol after co-administration of erlotinib were also observed. Copyright © 2017. Published by Elsevier B.V.

  20. Combined use of anti-ErbB monoclonal antibodies and erlotinib enhances antibody-dependent cellular cytotoxicity of wild-type erlotinib-sensitive NSCLC cell lines

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    Cavazzoni Andrea

    2012-12-01

    Full Text Available Abstract Background The epidermal growth factor receptor (EGFR is an established target for anti-cancer treatment in different tumour types. Two different strategies have been explored to inhibit this pivotal molecule in epithelial cancer development: small molecules TKIs and monoclonal antibodies. ErbB/HER-targeting by monoclonal antibodies such as cetuximab and trastuzumab or tyrosine-kinase inhibitors as gefitinib or erlotinib has been proven effective in the treatment of advanced NSCLC. Results In this study we explored the potential of combining either erlotinib with cetuximab or trastuzumab to improve the efficacy of EGFR targeted therapy in EGFR wild-type NSCLC cell lines. Erlotinib treatment was observed to increase EGFR and/or HER2 expression at the plasma membrane level only in NSCLC cell lines sensitive to the drug inducing protein stabilization. The combined treatment had marginal effect on cell proliferation but markedly increased antibody-dependent, NK mediated, cytotoxicity in vitro. Moreover, in the Calu-3 xenograft model, the combination significantly inhibited tumour growth when compared with erlotinib and cetuximab alone. Conclusion Our results indicate that erlotinib increases surface expression of EGFR and/or HER2 only in EGFR-TKI sensitive NSCLC cell lines and, in turns, leads to increased susceptibility to ADCC both in vitro and in a xenograft models. The combination of erlotinib with monoclonal antibodies represents a potential strategy to improve the treatment of wild-type EGFR NSCLC patients sensitive to erlotinib.

  1. Distribution of erlotinib in rash and normal skin in cancer patients receiving erlotinib visualized by matrix assisted laser desorption/ionization mass spectrometry imaging.

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    Nishimura, Meiko; Hayashi, Mitsuhiro; Mizutani, Yu; Takenaka, Kei; Imamura, Yoshinori; Chayahara, Naoko; Toyoda, Masanori; Kiyota, Naomi; Mukohara, Toru; Aikawa, Hiroaki; Fujiwara, Yasuhiro; Hamada, Akinobu; Minami, Hironobu

    2018-04-06

    The development of skin rashes is the most common adverse event observed in cancer patients treated with epidermal growth factor receptor-tyrosine kinase inhibitors such as erlotinib. However, the pharmacological evidence has not been fully revealed. Erlotinib distribution in the rashes was more heterogeneous than that in the normal skin, and the rashes contained statistically higher concentrations of erlotinib than adjacent normal skin in the superficial skin layer (229 ± 192 vs. 120 ± 103 ions/mm 2 ; P = 0.009 in paired t -test). LC-MS/MS confirmed that the concentration of erlotinib in the skin rashes was higher than that in normal skin in the superficial skin layer (1946 ± 1258 vs. 1174 ± 662 ng/cm 3 ; P = 0.028 in paired t -test). The results of MALDI-MSI and LC-MS/MS were well correlated (coefficient of correlation 0.879, P distribution of erlotinib in the skin tissue was visualized using non-labeled MALDI-MSI. Erlotinib concentration in the superficial layer of the skin rashes was higher than that in the adjacent normal skin. We examined patients with advanced pancreatic cancer who developed skin rashes after treatment with erlotinib and gemcitabine. We biopsied both the rash and adjacent normal skin tissues, and visualized and compared the distribution of erlotinib within the skin using matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI-MSI). The tissue concentration of erlotinib was also measured by liquid chromatography-tandem mass spectrometry (LC-MS/MS) with laser microdissection.

  2. Erlotinib augmentation with dapsone for rash mitigation and increased anti-cancer effectiveness.

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    Kast, R E

    2015-01-01

    The epidermal growth factor receptor tyrosine kinase inhibitor erlotinib has failed in many ways to be as potent in the anti-cancer role as pre-clinical studies would have suggested. This paper traces some aspects of this failure to a compensatory erlotinib-mediated increase in interleukin-8. Many other-but not all- cancer chemotherapeutic cytotoxic drugs also provoke a compensatory increase in a malignant clone's interleukin-8 synthesis. Untreated glioblastoma and other cancer cells themselves natively synthesize interleukin-8. Interleukin-8 has tumor growth promoting, mobility and metastasis formation enhancing, effects as well as pro-angiogenesis effects. The old sulfone antibiotic dapsone- one of the very first antibiotics in clinical use- has demonstrated several interleukin-8 system inhibiting actions. Review of these indicates dapsone has potential to augment erlotinib effectiveness. Erlotinib typically gives a rash that has recently been proven to come about via an erlotinib triggered up-regulated keratinocyte interleukin-8 synthesis. The erlotinib rash shares histological features reminiscent of typical neutrophilic dermatoses. Dapsone has an established therapeutic role in current treatment of other neutrophilic dermatoses. Thus, dapsone has potential to both improve the quality of life in erlotinib treated patients by amelioration of rash as well as to short-circuit a growth-enhancing aspect of erlotinib when used in the anti-cancer role.

  3. A case of new onset keratosis pilaris after discontinuation of erlotinib.

    Science.gov (United States)

    Okereke, Uchenna R; Colozza, Sara; Cohen, David E

    2014-11-01

    Keratosis pilaris and keratosis pilaris-like eruptions have been reported in association with RAF inhibitors sorafenib and vemurafenib. We describe herein what is to our knowledge the first reported case of new onset keratosis pilaris after discontinuation of EGFR inhibitor erlotinib. A 60 year-old female with stage IV lung cancer was treated with erlotinib (100 mg/d). The patient elected to discontinue erlotinib after four years secondary to adverse systemic reactions. However, five months later small, monomorphic, rough, folliculocentric papules with surrounding mild erythema characteristic of keratosis pilaris were noted on upper back and arms. This serves as the first documented case of new onset keratosis pilaris in a patient after discontinuation of erlotinib. We report the present case to show the possible association of keratosis pilaris with not only RAF inhibitors, but also the EGFR inhibitor erlotinib. Further investigation will determine whether this is a class effect with other systemic EGFR inhibitors.

  4. Erlotinib Versus Radiation Therapy for Brain Metastases in Patients With EGFR-Mutant Lung Adenocarcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Gerber, Naamit K.; Yamada, Yoshiya; Rimner, Andreas [Department of Radiation Oncology, Memorial Sloan-Kettering Cancer Center, New York, New York (United States); Shi, Weiji [Department of Epidemiology and Biostatistics, Memorial Sloan-Kettering Cancer Center, New York, New York (United States); Riely, Gregory J. [Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York, New York (United States); Beal, Kathryn [Department of Radiation Oncology, Memorial Sloan-Kettering Cancer Center, New York, New York (United States); Yu, Helena A. [Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York, New York (United States); Chan, Timothy A. [Department of Radiation Oncology, Memorial Sloan-Kettering Cancer Center, New York, New York (United States); Zhang, Zhigang [Department of Epidemiology and Biostatistics, Memorial Sloan-Kettering Cancer Center, New York, New York (United States); Wu, Abraham J., E-mail: wua@mskcc.org [Department of Radiation Oncology, Memorial Sloan-Kettering Cancer Center, New York, New York (United States)

    2014-06-01

    Purpose/Objectives: Radiation therapy (RT) is the principal modality in the treatment of patients with brain metastases (BM). However, given the activity of EGFR tyrosine kinase inhibitors in the central nervous system, it is uncertain whether upfront brain RT is necessary for patients with EGFR-mutant lung adenocarcinoma with BM. Methods and Materials: Patients with EGFR-mutant lung adenocarcinoma and newly diagnosed BM were identified. Results: 222 patients were identified. Exclusion criteria included prior erlotinib use, presence of a de novo erlotinib resistance mutation, or incomplete data. Of the remaining 110 patients, 63 were treated with erlotinib, 32 with whole brain RT (WBRT), and 15 with stereotactic radiosurgery (SRS). The median overall survival (OS) for the whole cohort was 33 months. There was no significant difference in OS between the WBRT and erlotinib groups (median, 35 vs 26 months; P=.62), whereas patients treated with SRS had a longer OS than did those in the erlotinib group (median, 64 months; P=.004). The median time to intracranial progression was 17 months. There was a longer time to intracranial progression in patients who received WBRT than in those who received erlotinib upfront (median, 24 vs 16 months, P=.04). Patients in the erlotinib or SRS group were more likely to experience intracranial failure as a component of first failure, whereas WBRT patients were more likely to experience failure outside the brain (P=.004). Conclusions: The survival of patients with EGFR-mutant adenocarcinoma with BM is notably long, whether they receive upfront erlotinib or brain RT. We observed longer intracranial control with WBRT, even though the WBRT patients had a higher burden of intracranial disease. Despite the equivalent survival between the WBRT and erlotinib group, this study underscores the role of WBRT in producing durable intracranial control in comparison with a targeted biologic agent with known central nervous system activity.

  5. Radiation recall gastritis secondary to erlotinib in a patient with pancreatic cancer.

    Science.gov (United States)

    Graziani, Casey; Hegde, Sanjay; Saif, Muhammad Wasif

    2014-12-01

    Radiation recall refers to chemotherapy-triggered inflammation in healthy areas previously exposed to irradiation. Chemotherapeutics known to be associated with radiation recall phenomenon include anthracyclines, taxanes and antimetabolites, such as gemcitabine and capecitabine. Case reports detailing radiation recall dermatitis and pneumonitis associated with erlotinib have been previously described in the literature, however, there are no reported cases describing radiation gastritis associated with erlotinib. We report a patient with pancreatic cancer who developed gastrointestinal bleeding secondary to radiation recall gastritis related to erlotinib exposure. A 57-year-old Hispanic male with pancreatic cancer initially received 7 cycles of FOLFIRINOX followed by capecitabine with radiation therapy for 28 fractions for a total of 5,040 cGy. Re-staging with computed tomography demonstrated stable disease. The patient was then treated with erlotinib and capecitabine for approximately two months before restaging demonstrated progressive disease. Shortly after discontinuing erlotinib and capecitabine, the patient reported maroon colored stools. Laboratory studies demonstrated a precipitous drop in hemoglobin and hematocrit from pre-treatment baseline, ultimately requiring transfusion with packed red blood cells. Subsequent esophagogastroduodenoscopy demonstrated findings consistent with radiation gastritis, with oozing in the gastric body and antrum, which was treated therapeutically with argon plasma coagulation. The patient's gastrointestinal bleed was difficult to control. Over the course of a two-month period - the patient required multiple admissions, repeat therapeutic esophagogastroduodenoscopies and transfusions. Radiation recall from erlotinib is rare but can potentially arise in any site that has been previously irradiated. There may be an association between the pathogenesis of radiation recall and erlotinib's up-regulation of the angiogenic growth factor

  6. Clinical aspects and perspectives of erlotinib in the treatment of patients with biliary tract cancer

    DEFF Research Database (Denmark)

    Jensen, Lars Henrik

    2016-01-01

    INTRODUCTION: Patients with non-resectable biliary tract cancer have a poor prognosis even if treated with systemic chemotherapy. One hope for improving treatment is through molecular biology and the characterization of specific cancer driving alterations followed by the design of targeted drugs...... of patients benefitting from erlotinib. Until this subgroup has been defined, erlotinib has no value to biliary tract cancer patients in the daily clinic....

  7. Erlotinib is a viable treatment for tumors with acquired resistance to cetuximab

    Science.gov (United States)

    Brand, Toni M; Dunn, Emily F; Iida, Mari; Myers, Rebecca A; Kostopoulos, Kellie T; Li, Chunrong; Peet, Chimera R

    2011-01-01

    The epidermal growth factor receptor (EGFR) is an ubiquitously expressed receptor tyrosine kinase (RTK) and is recognized as a key mediator of tumorigenesis in many human tumors. Currently there are five EGFR inhibitors used in oncology, two monoclonal antibodies (panitumumab and cetuximab) and three tyrosine kinase inhibitors (erlotinib, gefitinib and lapatinib). Both strategies of EGFR inhibition have demonstrated clinical success; however, many tumors remain non-responsive or acquire resistance during therapy. To explore potential molecular mechanisms of acquired resistance to cetuximab we previously established a series of cetuximab-resistant clones by chronically exposing the NCI-H226 NSCLC cell line to escalating doses of cetuximab. Cetuximab-resistant clones exhibited a dramatic increase in the activation of EGFR, HER2 and HER3 receptors as well as increased signaling through the MAP K and AKT pathways. RNAi studies demonstrated dependence of cetuximab-resistant clones on the EGFR signaling network. These findings prompted investigation on whether or not cells with acquired resistance to cetuximab would be sensitive to the EGFR targeted TKI erlotinib. In vitro, erlotinib was able to decrease signaling through the EGFR axis, decrease cellular proliferation and induce apoptosis. To determine if erlotinib could have therapeutic benefit in vivo, we established cetuximab-resistant NCI-H226 mouse xenografts, and subsequently treated them with erlotinib. Mice harboring cetuximab-resistant tumors treated with erlotinib exhibited either a tumor regression or growth delay as compared with vehicle controls. Analysis of the erlotinib treated tumors demonstrated a decrease in cell proliferation and increased rates of apoptosis. The work presented herein suggests that (1) cells with acquired resistance to cetuximab maintain their dependence on EGFR and (2) tumors developing resistance to cetuximab can benefit from subsequent treatment with erlotinib, providing rationale

  8. Erlotinib-loaded albumin nanoparticles: A novel injectable form of erlotinib and its in vivo efficacy against pancreatic adenocarcinoma ASPC-1 and PANC-1 cell lines.

    Science.gov (United States)

    Noorani, M; Azarpira, N; Karimian, K; Heli, H

    2017-10-05

    Erlotinib was loaded on albumin nanoparticles for the first time and the cytotoxic effect of the resulting nanoparticles against ASPC-1 and PANC-1 pancreatic adenocarcinoma cell lines was evaluated. The carrier (albumin nanoparticles, ANPs) was synthesized by desolvation method using a mixed solvent followed by thermal crosslinking for stabilization. ANPs and the drug-loaded ANPs were characterized by field emission scanning and transmission electron microscopies, particle size analysis and Fourier transform infrared spectroscopy. The nanoformulation had a size of PANC-1 cell line). Values of IC 50 were obtained for both cell lines and indicated significant reduction in the erlotinib dose necessary for killing the cells, while, ANPs were completely safe. The results demonstrated that erlotinib-loaded ANPs had a remarkable potential for pancreatic cancer drug delivery. Copyright © 2017 Elsevier B.V. All rights reserved.

  9. Sequentially administrated of pemetrexed with icotinib/erlotinib in lung adenocarcinoma cell lines in vitro.

    Science.gov (United States)

    Feng, Xiuli; Zhang, Yan; Li, Tao; Li, Yu

    2017-12-26

    Combination of chemotherapy and epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) had been proved to be a potent anti-drug for the treatment of tumors. However, survival time was not extended for the patients with lung adenocarcinoma (AdC) compared with first-line chemotherapy. In the present study, we attempt to assess the optimal schedule of the combined administration of pemetrexed and icotinib/erlotinib in AdC cell lines. Human lung AdC cell lines with wild-type (A549), EGFR T790M (H1975) and activating EGFR mutation (HCC827) were applied in vitro to assess the differential efficacy of various sequential regimens on cell viability, cell apoptosis and cell cycle distribution. The results suggested that the antiproliferative effect of the sequence of pemetrexed followed by icotinib/erlotinib was more effective than that of icotinib/erlotinib followed by pemetrexed. Additionally, a reduction of G1 phase and increased S phase in sequence of pemetrexed followed by icotinib/erlotinib was also observed, promoting cell apoptosis. Thus, the sequential administration of pemetrexed followed by icotinib/erlotinib exerted a synergistic effect on HCC827 and H1975 cell lines compared with the reverse sequence. The sequential treatment of pemetrexed followed by icotinib/erlotinib has been demonstrated promising results. This treatment strategy warrants further confirmation in patients with advanced lung AdC.

  10. The concentration of erlotinib in the cerebrospinal fluid of patients with brain metastasis from non-small-cell lung cancer

    Science.gov (United States)

    DENG, YANMING; FENG, WEINENG; WU, JING; CHEN, ZECHENG; TANG, YICONG; ZHANG, HUA; LIANG, JIANMIAO; XIAN, HAIBING; ZHANG, SHUNDA

    2014-01-01

    It has been demonstrated that erlotinib is effective in treating patients with brain metastasis from non-small-cell lung cancer. However, the number of studies determining the erlotinib concentration in these patients is limited. The purpose of this study was to measure the concentration of erlotinib in the cerebrospinal fluid of patients with brain metastasis from non-small-cell lung carcinoma. Six patients were treated with the standard recommended daily dose of erlotinib (150 mg) for 4 weeks. All the patients had previously received chemotherapy, but no brain radiotherapy. At the end of the treatment period, blood plasma and cerebrospinal fluid samples were collected and the erlotinib concentration was determined by high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS). The average erlotinib concentration in the blood plasma and the cerebrospinal fluid was 717.7±459.7 and 23.7±13.4 ng/ml, respectively. The blood-brain barrier permeation rate of erlotinib was found to be 4.4±3.2%. In patients with partial response (PR), stable disease (SD) and progressive disease (PD), the average concentrations of erlotinib in the cerebrospinal fluid were 35.5±19.0, 19.1±8.7 and 16.4±5.9 ng/ml, respectively. In addition, the efficacy rate of erlotinib for metastatic brain lesions was 33.3%, increasing to 50% in patients with EGFR mutations. However, erlotinib appeared to be ineffective in cases with wild-type EGFR. In conclusion, a relatively high concentration of erlotinib was detected in the cerebrospinal fluid of patients with brain metastases from non-small-cell lung cancer. Thus, erlotinib may be considered as a treatment option for this patient population. PMID:24649318

  11. The intestinotrophic peptide, GLP-2, counteracts the gastrointestinal atrophy in mice induced by the epidermal growth factor receptor inhibitor, erlotinib, and cisplatin

    DEFF Research Database (Denmark)

    Rasmussen, Andreas Rosén; Viby, Niels-Erik; Hare, Kristine Juul

    2010-01-01

    Erlotinib, an epidermal-growth-factor receptor inhibitor, belongs to a new generation of targeted cancer therapeutics. Gastrointestinal side-effects are common and have been markedly aggravated when erlotinib is combined with cytostatics. We examined the effects of erlotinib alone and combined wi...

  12. Spontaneous Healing of Corneal Perforation after Temporary Discontinuation of Erlotinib Treatment

    Directory of Open Access Journals (Sweden)

    Naoyuki Morishige

    2014-01-01

    Full Text Available Purpose: To report a case of corneal perforation associated with oral administration of erlotinib and its spontaneous healing after temporary discontinuation of drug treatment. Case Report: A 65-year-old man with metastatic lung cancer was treated with erlotinib (150 mg/day, a specific tyrosine kinase inhibitor of the epidermal growth factor receptor. He was referred to our corneal service for the treatment of bilateral corneal disorders, diagnosed with mild aqueous-deficient dry eye, and treated by insertion of punctal plugs. His corneal epithelial disorders initially improved, but subsequently worsened, as manifested by the development of bilateral corneal ulceration with corneal perforation in the right eye. The oral administration of erlotinib was interrupted in preparation for tectonic keratoplasty, but 2 days later the corneal perforation of the right eye and the bilateral epithelial defects had healed spontaneously. Treatment with erlotinib was resumed at half the initial dose, and the cornea of both eyes has remained apparently healthy. Discussion: Erlotinib may be secreted into tear fluid and thereby adversely affect the corneal epithelium. The development of corneal epithelial disorders in patients receiving this drug may be reversed by reducing its dose.

  13. A phase I evaluation of the combination of vinflunine and erlotinib in patients with refractory solid tumors

    Science.gov (United States)

    Sanoff, Hanna K.; Davies, Janine M.; Walko, Christine; Irvin, William; Buie, Larry; Keller, Kimberly; Ivanova, Anastasia; Chiu, Wing-Keung; O'Neil, Bert H.; Stinchcombe, Thomas E.

    2010-01-01

    Summary Purpose Epidermal growth factor receptor (EGFR) inhibition may overcome chemotherapy resistance by inhibiting important anti-apoptotic signals that are constitutively activated by an overstimulated EGFR pathway. Methods This phase I dose escalation trial assessed the safety and efficacy of vinflunine, a novel vinca alkaloid microtubule inhibitor, with erlotinib, an EGFR tyrosine kinase inhibitor, in patients with refractory solid tumors. Results Seventeen patients were treated, 10 with continuous erlotinib, and 7 with intermittent erlotinib. At dose level 1, vinflunine 280 mg/m2 IV day 1 and erlotinib 75 mg PO days 2–21 (“continuous erlotinib”) in 21 day cycles, two of four patients experienced DLTs. At dose level -1 (vinflunine 250 mg/m2 every 21 days and erlotinib 75 mg/day), two of six patients experienced DLTs. The study was amended to enroll to “intermittent erlotinib” dosing: vinflunine day 1 and erlotinib days 2–15 of a 21 day cycle. Two of seven experienced DLTs and the study was terminated. One patient with breast cancer had a partial response; three had stable disease ≥6 cycles. All were treated in the continuous erlotinib group. Conclusions Given the marked toxicity in our patient population, the combination of vinflunine and erlotinib cannot be recommended for further study with these dosing schemas. PMID:20387090

  14. Schedule-dependent cytotoxic synergism of pemetrexed and erlotinib in BXPC-3 and PANC-1 human pancreatic cancer cells.

    Science.gov (United States)

    Wang, Lin; Zhu, Zhi-Xia; Zhang, Wen-Ying; Zhang, Wei-Min

    2011-09-01

    Previous studies have shown that both pemetrexed, a cytotoxic drug, and erlotinib, an epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI), inhibit the cell growth of pancreatic cancer cells. However, whether they exert a synergistic antitumor effect on pancreatic cancer cells remains unknown. The present study aimed to assess the synergistic effect of erlotinib in combination with pemetrexed using different sequential administration schedules on the proliferation of human pancreatic cancer BXPC-3 and PANC-1 cells and to probe its cellular mechanism. The EGFR and K-ras gene mutation status was examined by quantitative PCR high-resolution melting (qPCR-HRM) analysis. BXPC-3 and PANC-1 cells were incubated with pemetrexed and erlotinib using different administration schedules. MTT assay was used to determine cytotoxicity, and cell cycle distribution was determined by flow cytometry. The expression and phosphorylation of EGFR, HER3, AKT and MET were determined using Western blotting. Both pemetrexed and erlotinib inhibited the proliferation of BXPC-3 and PANC-1 cells in a dose- and time-dependent manner in vitro. Synergistic effects on cell proliferation were observed when pemetrexed was used in combination with erlotinib. The degree of the synergistic effects depended on the administration sequence, which was most obvious when erlotinib was sequentially administered at 24-h interval following pemetrexed. Cell cycle studies revealed that pemetrexed induced S arrest and erlotinib induced G(0)/G(1) arrest. The sequential administration of erlotinib following pemetrexed induced S arrest. Western blot analyses showed that pemetrexed increased and erlotinib decreased the phosphorylation of EGFR, HER3 and AKT, respectively. However, both pemetrexed and erlotinib exerted no significant effects on the phosphorylation of c-MET. The phosphorylation of EGFR, HER3 and AKT was significantly suppressed by scheduled incubation with pemetrexed followed by erlotinib

  15. Role of ATP-binding cassette and solute carrier transporters in erlotinib CNS penetration and intracellular accumulation.

    Science.gov (United States)

    Elmeliegy, Mohamed A; Carcaboso, Angel M; Tagen, Michael; Bai, Feng; Stewart, Clinton F

    2011-01-01

    To study the role of drug transporters in central nervous system (CNS) penetration and cellular accumulation of erlotinib and its metabolite, OSI-420. After oral erlotinib administration to wild-type and ATP-binding cassette (ABC) transporter-knockout mice (Mdr1a/b(-/-), Abcg2(-/-), Mdr1a/b(-/-)Abcg2(-/-), and Abcc4(-/-)), plasma was collected and brain extracellular fluid (ECF) was sampled using intracerebral microdialysis. A pharmacokinetic model was fit to erlotinib and OSI-420 concentration-time data, and brain penetration (P(Brain)) was estimated by the ratio of ECF-to-unbound plasma area under concentration-time curves. Intracellular accumulation of erlotinib was assessed in cells overexpressing human ABC transporters or SLC22A solute carriers. P(Brain) in wild-type mice was 0.27 ± 0.11 and 0.07 ± 0.02 (mean ± SD) for erlotinib and OSI-420, respectively. Erlotinib and OSI-420 P(Brain) in Abcg2(-/-) and Mdr1a/b(-/-)Abcg2(-/-) mice were significantly higher than in wild-type mice. Mdr1a/b(-/-) mice showed similar brain ECF penetration as wild-type mice (0.49 ± 0.37 and 0.04 ± 0.02 for erlotinib and OSI-420, respectively). In vitro, erlotinib and OSI-420 accumulation was significantly lower in cells overexpressing breast cancer resistance protein (BCRP) than in control cells. Only OSI-420, not erlotinib, showed lower accumulation in cells overexpressing P-glycoprotein (P-gp) than in control cells. The P-gp/BCRP inhibitor elacridar increased erlotinib and OSI-420 accumulation in BCRP-overexpressing cells. Erlotinib uptake was higher in OAT3- and OCT2-transfected cells than in empty vector control cells. Abcg2 is the main efflux transporter preventing erlotinib and OSI-420 penetration in mouse brain. Erlotinib and OSI-420 are substrates for SLC22A family members OAT3 and OCT2. Our findings provide a mechanistic basis for erlotinib CNS penetration, cellular uptake, and efflux mechanisms. ©2010 AACR.

  16. Four Cases of Interstitial Lung Disease Induced by Erlotinib 
and A Review of the Literatures

    Directory of Open Access Journals (Sweden)

    Xiaoling WU

    2012-08-01

    Full Text Available Erlotinib is an agent of oral epidermal growth factor receptor (EGFR tyrosine kinase inhibitors which are used for non-small cell lung cancer. Although this class of agents is considered to be relatively safe, the most serious, but rare, adverse reaction is drug-associated interstitial lung disease (ILD. ILD induced by gefitinib been often described, but the ILD induced by erlotinib is relatively less well known. We here describle four cases of ILD related to erlotinib and review recent literatures to help physicians earlier alert erlotinib-induced ILD. It is important to carefully monitor pulmonary symptoms in all patients who are receiving erlotinib. Early diagnosis and timely intervention is critical in the treatment of drug-induced ILD.

  17. NOX4 mediates cytoprotective autophagy induced by the EGFR inhibitor erlotinib in head and neck cancer cells

    International Nuclear Information System (INIS)

    Sobhakumari, Arya; Schickling, Brandon M.; Love-Homan, Laurie; Raeburn, Ayanna; Fletcher, Elise V.M.; Case, Adam J.; Domann, Frederick E.; Miller, Francis J.

    2013-01-01

    Most head and neck squamous cell carcinomas (HNSCCs) overexpress epidermal growth factor receptor (EGFR) and EGFR inhibitors are routinely used in the treatment of HNSCC. However, many HNSCC tumors do not respond or become refractory to EGFR inhibitors. Autophagy, which is a stress-induced cellular self-degradation process, has been reported to reduce the efficacy of chemotherapy in various disease models. The purpose of this study is to determine if the efficacy of the EGFR inhibitor erlotinib is reduced by activation of autophagy via NOX4-mediated oxidative stress in HNSCC cells. Erlotinib induced the expression of the autophagy marker LC3B-II and autophagosome formation in FaDu and Cal-27 cells. Inhibition of autophagy by chloroquine and knockdown of autophagy pathway genes Beclin-1 and Atg5 sensitized both cell lines to erlotinib-induced cytotoxicity, suggesting that autophagy may serve as a protective mechanism. Treatment with catalase (CAT) and diphenylene iodonium (DPI) in the presence of erlotinib suppressed the increase in LC3B-II expression in FaDu and Cal-27 cells. Erlotinib increased NOX4 mRNA and protein expression by increasing its promoter activity and mRNA stability in FaDu cells. Knockdown of NOX4 using adenoviral siNOX4 partially suppressed erlotinib-induced LC3B-II expression, while overexpression of NOX4 increased expression of LC3B-II. These studies suggest that erlotinib may activate autophagy in HNSCC cells as a pro-survival mechanism, and NOX4 may play a role in mediating this effect. - Highlights: • Erlotinib increased LC3B-II and autophagosome formation in HNSCC cells. • Inhibition of autophagy sensitized HNSCC cells to erlotinib. • Erlotinib increased NOX4 promoter and 3′UTR luciferase activity. • Manipulating NOX4 decreases or increases autophagy

  18. NOX4 mediates cytoprotective autophagy induced by the EGFR inhibitor erlotinib in head and neck cancer cells

    Energy Technology Data Exchange (ETDEWEB)

    Sobhakumari, Arya [Interdisciplinary Graduate Program in Human Toxicology, The University of Iowa, Iowa City, IA (United States); Department of Pathology, The University of Iowa, Iowa City, IA (United States); Schickling, Brandon M. [Department of Internal Medicine, The University of Iowa, Iowa City, IA (United States); Love-Homan, Laurie; Raeburn, Ayanna [Department of Pathology, The University of Iowa, Iowa City, IA (United States); Fletcher, Elise V.M. [Interdisciplinary Graduate Program in Human Toxicology, The University of Iowa, Iowa City, IA (United States); Department of Pathology, The University of Iowa, Iowa City, IA (United States); Case, Adam J. [Free Radical and Radiation Biology Program, Department of Radiation Oncology, The University of Iowa, Iowa City, IA (United States); Domann, Frederick E. [Interdisciplinary Graduate Program in Human Toxicology, The University of Iowa, Iowa City, IA (United States); Department of Pathology, The University of Iowa, Iowa City, IA (United States); Free Radical and Radiation Biology Program, Department of Radiation Oncology, The University of Iowa, Iowa City, IA (United States); Holden Comprehensive Cancer Center, University of Iowa Hospitals and Clinics (UIHC), Iowa City, IA (United States); Miller, Francis J. [Department of Internal Medicine, The University of Iowa, Iowa City, IA (United States); Free Radical and Radiation Biology Program, Department of Radiation Oncology, The University of Iowa, Iowa City, IA (United States); Holden Comprehensive Cancer Center, University of Iowa Hospitals and Clinics (UIHC), Iowa City, IA (United States); and others

    2013-11-01

    Most head and neck squamous cell carcinomas (HNSCCs) overexpress epidermal growth factor receptor (EGFR) and EGFR inhibitors are routinely used in the treatment of HNSCC. However, many HNSCC tumors do not respond or become refractory to EGFR inhibitors. Autophagy, which is a stress-induced cellular self-degradation process, has been reported to reduce the efficacy of chemotherapy in various disease models. The purpose of this study is to determine if the efficacy of the EGFR inhibitor erlotinib is reduced by activation of autophagy via NOX4-mediated oxidative stress in HNSCC cells. Erlotinib induced the expression of the autophagy marker LC3B-II and autophagosome formation in FaDu and Cal-27 cells. Inhibition of autophagy by chloroquine and knockdown of autophagy pathway genes Beclin-1 and Atg5 sensitized both cell lines to erlotinib-induced cytotoxicity, suggesting that autophagy may serve as a protective mechanism. Treatment with catalase (CAT) and diphenylene iodonium (DPI) in the presence of erlotinib suppressed the increase in LC3B-II expression in FaDu and Cal-27 cells. Erlotinib increased NOX4 mRNA and protein expression by increasing its promoter activity and mRNA stability in FaDu cells. Knockdown of NOX4 using adenoviral siNOX4 partially suppressed erlotinib-induced LC3B-II expression, while overexpression of NOX4 increased expression of LC3B-II. These studies suggest that erlotinib may activate autophagy in HNSCC cells as a pro-survival mechanism, and NOX4 may play a role in mediating this effect. - Highlights: • Erlotinib increased LC3B-II and autophagosome formation in HNSCC cells. • Inhibition of autophagy sensitized HNSCC cells to erlotinib. • Erlotinib increased NOX4 promoter and 3′UTR luciferase activity. • Manipulating NOX4 decreases or increases autophagy.

  19. Identification of gene expression profiling associated with erlotinib-related skin toxicity in pancreatic adenocarcinoma patients

    Energy Technology Data Exchange (ETDEWEB)

    Caba, Octavio, E-mail: ocaba@ujaen.es [Department of Health Sciences, University of Jaen, Jaen (Spain); Irigoyen, Antonio, E-mail: antonioirigoyen@yahoo.com [Department of Medical Oncology, Virgen de la Salud Hospital, Toledo (Spain); Jimenez-Luna, Cristina, E-mail: crisjilu@ugr.es [Institute of Biopathology and Regenerative Medicine (IBIMER), Center of Biomedical Research (CIBM), University of Granada, Granada (Spain); Benavides, Manuel, E-mail: manuel.benavides.sspa@juntadeandalucia.es [Department of Medical Oncology, Virgen de la Victoria Hospital, Malaga (Spain); Ortuño, Francisco M., E-mail: fortuno@ugr.es [Department of Computer Architecture and Computer Technology, Research Center for Information and Communications Technologies, University of Granada, Granada (Spain); Gallego, Javier, E-mail: j.gallegoplazas@gmail.com [Department of Medical Oncology, General Universitario de Elche Hospital, Alicante (Spain); Rojas, Ignacio, E-mail: irojas@ugr.es [Department of Computer Architecture and Computer Technology, Research Center for Information and Communications Technologies, University of Granada, Granada (Spain); Guillen-Ponce, Carmen, E-mail: carmen.guillen@salud.madrid.org [Department of Medical Oncology, Ramón y Cajal University Hospital, Madrid (Spain); Torres, Carolina, E-mail: ctorres@uic.edu [Department of Medicine, Division of Gastroenterology and Hepatology, University of Illinois at Chicago, Chicago, IL (United States); Aranda, Enrique, E-mail: enrique.aranda@imibic.org [Maimonides Institute of Biomedical Research (IMIBIC), Reina Sofía Hospital, University of Córdoba, Córdoba (Spain); Prados, Jose, E-mail: jcprados@ugr.es [Institute of Biopathology and Regenerative Medicine (IBIMER), Center of Biomedical Research (CIBM), University of Granada, Granada (Spain)

    2016-11-15

    Erlotinib is an epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor that showed activity against pancreatic ductal adenocarcinoma (PDAC). The drug's most frequently reported side effect as a result of EGFR inhibition is skin rash (SR), a symptom which has been associated with a better therapeutic response to the drug. Gene expression profiling can be used as a tool to predict which patients will develop this important cutaneous manifestation. The aim of the present study was to identify which genes may influence the appearance of SR in PDAC patients. The study included 34 PDAC patients treated with erlotinib: 21 patients developed any grade of SR, while 13 patients did not (controls). Before administering any chemotherapy regimen and the development of SR, we collected RNA from peripheral blood samples of all patients and studied the differential gene expression pattern using the Illumina microarray platform HumanHT-12 v4 Expression BeadChip. Seven genes (FAM46C, IFITM3, GMPR, DENND6B, SELENBP1, NOL10, and SIAH2), involved in different pathways including regulatory, migratory, and signalling processes, were downregulated in PDAC patients with SR. Our results suggest the existence of a gene expression profiling significantly correlated with erlotinib-induced SR in PDAC that could be used as prognostic indicator in this patients. - Highlights: • Skin rash (SR) is the most characteristic side effect of erlotinib in PDAC patients. • Erlotinib-induced SR has been associated with a better clinical outcome. • Gene expression profiling was used to determine who will develop this manifestation. • 7 genes involved in different pathways were downregulated in PDAC patients with SR. • Our profile correlated with erlotinib-induced SR in PDAC could be used for prognosis.

  20. Erlotinib: Um caso clínico de sucesso e algumas notas sobre a toxicidade hepática

    Directory of Open Access Journals (Sweden)

    Agostinho Costa

    2008-10-01

    Full Text Available Resumo: Apresenta-se o caso clínico de uma mulher com adenocarcinoma do pulmão em que se conseguiu o controlo da doença, durante quinze meses, com erlotinib em segunda linha. Cerca de cinco meses após o início do tratamento ocorreu hiperbilirrubinemia isolada de grau 3, que motivou a redução da dose para 100 mg/dia. A este propósito, fazem-se alguns comentários sobre a toxicidade hepática do erlotinib e sobre o efeito das interacções farmacológicas no seu metabolismo.Rev Port Pneumol 2008; XIV (Supl 3: S29-S34 Abstract: A case of a woman with lung adenocarcinoma in which fifteen-month disease control was achieved with second-line erlotinib treatment is presented. Five months after treatment beginning, isolated grade 3 hyperbilirubinemia occurred and daily dose was reduced to 100 mg. Comments on erlotinib hepatic toxicity and the pharmacologic interactions on erlotinib metabolism are given.Rev Port Pneumol 2008; XIV (Supl 3: S29-S34 Palavras-chave: Erlotinib, toxicidade hepática, hiperbilirrubinemia, interacções farmacológicas, Key-words: Erlotinib, hepatic toxicity, hyperbilirubinemia, pharmacologic interactions

  1. Fisetin, a dietary phytochemical, overcomes Erlotinib-resistance of lung adenocarcinoma cells through inhibition of MAPK and AKT pathways.

    Science.gov (United States)

    Zhang, Liang; Huang, Yi; Zhuo, Wenlei; Zhu, Yi; Zhu, Bo; Chen, Zhengtang

    2016-01-01

    Erlotinib (Tarceva) is a selective epidermal growth factor receptor tyrosine kinase inhibitor for treatment of non-small cell lung cancer (NSCLC). However, its efficacy is usually reduced by the occurrence of drug resistance. Our recent study showed that a flavonoid found in many plants, Fisetin, might have a potential to reverse the acquired Cisplatin-resistance of lung adenocarcinoma. In the present study, we aimed to test whether Fisetin could have the ability to reverse Erlotinib-resistance of lung cancer cells. Erlotinib-resistant lung adenocarcinoma cells, HCC827-ER, were cultured from the cell line HCC827, and the effects of Fisetin and Erlotinib on the cell viability and apoptosis were evaluated. The possible signaling pathways in this process were also detected. As expected, the results showed that Fisetin effectively increased sensitivity of Erlotinib-resistant lung cancer cells to Erlotinib, possibly by inhibiting aberrant activation of MAPK and AKT signaling pathways resulted from AXL suppression. In conclusion, Fisetin was a potential agent for reversing acquired Erlotinib-resistance of lung adenocarcinoma. Inactivation of AXL, MAPK and AKT pathways might play a partial role in this process.

  2. A Modeling and Simulation Framework for Adverse Events in Erlotinib-Treated Non-Small-Cell Lung Cancer Patients.

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    Suleiman, Ahmed Abbas; Frechen, Sebastian; Scheffler, Matthias; Zander, Thomas; Nogova, Lucia; Kocher, Martin; Jaehde, Ulrich; Wolf, Jürgen; Fuhr, Uwe

    2015-11-01

    Treatment with erlotinib, an epidermal growth factor receptor tyrosine kinase inhibitor used for treating non-small-cell lung cancer (NSCLC) and other cancers, is frequently associated with adverse events (AE). We present a modeling and simulation framework for the most common erlotinib-induced AE, rash, and diarrhea, providing insights into erlotinib toxicity. We used the framework to investigate the safety of high-dose erlotinib pulses proposed to limit acquired resistance while treating NSCLC. Continuous-time Markov models were developed using rash and diarrhea AE data from 39 NSCLC patients treated with erlotinib (150 mg/day). Exposure and different covariates were investigated as predictors of variability. Rash was also tested as a survival predictor. Models developed were used in a simulation analysis to compare the toxicities of different regimens, including the previously mentioned pulsed strategy. Probabilities of experiencing rash or diarrhea were found to be highest early during treatment. Rash, but not diarrhea, was positively correlated with erlotinib exposure. In contrast with some common understandings, radiotherapy decreased transitioning to higher rash grades by 81% (p simulations predicted that the proposed pulsed regimen (1600 mg/week + 50 mg/day remaining week days) results in a maximum of 20% of the patients suffering from severe rash throughout the treatment course in comparison to 12% when treated with standard dosing (150 mg/day). In conclusion, the framework demonstrated that radiotherapy attenuates erlotinib-induced rash, providing an opportunity to use radiotherapy and erlotinib together, and demonstrated the tolerability of high-dose pulses intended to address acquired resistance to erlotinib.

  3. Management of advanced pancreatic cancer with gemcitabine plus erlotinib: efficacy and safety results in clinical practice.

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    Diaz Beveridge, Robert; Alcolea, Vicent; Aparicio, Jorge; Segura, Ángel; García, Jose; Corbellas, Miguel; Fonfría, María; Giménez, Alejandra; Montalar, Joaquin

    2014-01-10

    The combination of gemcitabine and erlotinib is a standard first-line treatment for unresectable, locally advanced or metastatic pancreatic cancer. We reviewed our single centre experience to assess its efficacy and toxicity in clinical practice. Clinical records of patients with unresectable, locally advanced or metastatic pancreatic cancer who were treated with the combination of gemcitabine and erlotinib were reviewed. Univariate survival analysis and multivariate analysis were carried out to indentify independent predictors factors of overall survival. Our series included 55 patients. Overall disease control rate was 47%: 5% of patients presented complete response, 20% partial response and 22% stable disease. Median overall survival was 8.3 months). Cox regression analysis indicated that performance status and locally advanced versus metastatic disease were independent factors of overall survival. Patients who developed acne-like rash toxicity, related to erlotinib administration, presented a higher survival than those patients who did not develop this toxicity. Gemcitabine plus erlotinib doublet is active in our series of patients with advanced pancreatic cancer. This study provides efficacy and safety results similar to those of the pivotal phase III clinical trial that tested the same combination.

  4. Phase II trial of second-line erlotinib and digoxin for nonsmall cell lung cancer (NSCLC

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    Fadi Kayali

    2011-02-01

    Full Text Available Fadi Kayali, Muhamad A Janjua, Damian A Laber, Donald Miller, Goetz H KloeckerUniversity of Louisville, James Graham Brown Cancer Center, Louisville, KY, USABackground: In vitro digoxin sensitizes cancer cells to the induction of apoptosis by chemotherapy. Inhibition of the Na/K-ATPase enzyme by ouabain disturbs the intracellular ion composition of cancer cells, altering cellular homeostasis. This suggests that inhibition of the Na/K pump results in cellular sensitization of malignant but not benign cells to the induction of apoptosis. Epidemiologic studies have also shown beneficial effects of digitalis in breast cancer incidence. At ASCO (American Society of Clinical Oncology 2007 our group presented a Phase II study showing encouraging results by adding digoxin to biochemotherapy for melanoma. Erlotinib is one of the standard second-line treatments for nonsmall cell lung cancer (NSCLC, with a response rate (RR of 10%. This study's hypothesis was that adding digoxin to erlotinib will improve the RR and time to progression (TTP in NSCLC.Methods: Patients with progressive disease (PD after chemotherapy were enrolled if they had an ECOG (Eastern Cooperative Oncology Group score from 0 to 2 and good organ function. Daily erlotinib 150 mg and digoxin 0.25 mg were taken by mouth. The digoxin dose was adjusted to keep levels between 1 and 2 ng/mL. Computed tomography scans were done every 6 weeks. Treatment continued until PD or significant toxicity occurred.Results: Patient accrual lasted from March 2006 until August 2008 and was stopped early at the time of interim analysis. Twenty-eight patients were enrolled, and 24 who completed at least 6 weeks of therapy are presented here. All patients had unresectable NSCLC stage III/IV at diagnosis. Median age was 61 (34–78, 14 were female, 17 had prior radiation (not involving the target lesions, 23 had one prior chemotherapy, and one subject had two. Only one patient was a never-smoker. Histologies were

  5. Results From the Phase III Randomized Trial of Onartuzumab Plus Erlotinib Versus Erlotinib in Previously Treated Stage IIIB or IV Non-Small-Cell Lung Cancer: METLung.

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    Spigel, David R; Edelman, Martin J; O'Byrne, Kenneth; Paz-Ares, Luis; Mocci, Simonetta; Phan, See; Shames, David S; Smith, Dustin; Yu, Wei; Paton, Virginia E; Mok, Tony

    2017-02-01

    Purpose The phase III OAM4971g study (METLung) examined the efficacy and safety of onartuzumab plus erlotinib in patients with locally advanced or metastatic non-small-cell lung cancer selected by MET immunohistochemistry whose disease had progressed after treatment with a platinum-based chemotherapy regimen. Patients and Methods Patients were randomly assigned at a one-to-one ratio to receive onartuzumab (15 mg/kg intravenously on day 1 of each 21-day cycle) plus daily oral erlotinib 150 mg or intravenous placebo plus daily oral erlotinib 150 mg. The primary end point was overall survival (OS) in the intent-to-treat population. Secondary end points included median progression-free survival, overall response rate, biomarker analysis, and safety. Results A total of 499 patients were enrolled (onartuzumab, n = 250; placebo, n = 249). Median OS was 6.8 versus 9.1 months for onartuzumab versus placebo (stratified hazard ratio [HR], 1.27; 95% CI, 0.98 to 1.65; P = .067), with a greater number of deaths in the onartuzumab arm (130 [52%] v 114 [46%]). Median progression-free survival was 2.7 versus 2.6 months (stratified HR, 0.99; 95% CI, 0.81 to 1.20; P = .92), and overall response rate was 8.4% and 9.6% for onartuzumab versus placebo, respectively. Exploratory analyses using MET fluorescence in situ hybridization status and gene expression showed no benefit for onartuzumab; patients with EGFR mutations showed a trend toward shorter OS with onartuzumab treatment (HR, 4.68; 95% CI, 0.97 to 22.63). Grade 3 to 5 adverse events were reported by 56.0% and 51.2% of patients, with serious AEs in 33.9% and 30.7%, for experimental versus control arms, respectively. Conclusion Onartuzumab plus erlotinib did not improve clinical outcomes, with shorter OS in the onartuzumab arm, compared with erlotinib in patients with MET-positive non-small-cell lung cancer.

  6. Phase II trial of epidermal growth factor ointment for patients with Erlotinib-related skin effects.

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    Hwang, In Gyu; Kang, Jung Hun; Oh, Sung Yong; Lee, Suee; Kim, Sung-Hyun; Song, Ki-Hoon; Son, Choonhee; Park, Min Jae; Kang, Myung Hee; Kim, Hoon Gu; Lee, Jeeyun; Park, Young Suk; Sun, Jong Mu; Kim, Hyun Jung; Kim, Chan Kyu; Yi, Seong Yoon; Jang, Joung-Soon; Park, Keunchil; Kim, Hyo-Jin

    2016-01-01

    The efficacy of erlotinib, the epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor, has been demonstrated in patients with non-small cell lung cancer (NSCLC) and pancreatic cancer (PC). In the present study, we evaluated the effect of epidermal growth factor (EGF) ointment on erlotinib-related skin effects (ERSEs). This was an open-label, non-comparative, multicenter, phase II trial. The patients included those diagnosed with NSCLC or PC who were treated with erlotinib. The effectiveness of the ointment was defined as follows: (1) grade 2, 3, or 4 ERSEs downgraded to ≤ grade 1 or (2) grade 3 or 4 ERSEs downgraded to grade 2 and persisted for at least 2 weeks. Fifty-two patients from seven institutes in Korea were enrolled with informed consent. The final assessment included 46 patients (30 males, 16 females). According to the definition of effectiveness, the EGF ointment was effective in 36 (69.2%) intention to treat patients. There were no statistically significant differences in the effectiveness of the EGF ointment by gender (p = 0.465), age (p = 0.547), tumor type (p = 0.085), erlotinib dosage (p = 0.117), and number of prior chemotherapy sessions (p = 0.547). The grading for the average National Cancer Institute's Common Terminology Criteria for Adverse Events (NCI-CTCAE) rating of rash/acne and itching improved from 2.02 ± 0.83 to 1.13 ± 0.89 and 1.52 ± 0.84 to 0.67 ± 0.90, respectively (p reason for discontinuing the study was progression of cancer (37%). Based on the results, the EGF ointment is effective for ERSEs, regardless of gender, age, type of tumor, and dosage of erlotinib. The EGF ointment evenly improved all kinds of symptoms of ERSEs. ClinicalTrials.gov identifier: NCT01593995.

  7. Dose escalation to rash for erlotinib plus gemcitabine for metastatic pancreatic cancer: the phase II RACHEL study.

    Science.gov (United States)

    Van Cutsem, E; Li, C-P; Nowara, E; Aprile, G; Moore, M; Federowicz, I; Van Laethem, J-L; Hsu, C; Tham, C K; Stemmer, S M; Lipp, R; Zeaiter, A; Fittipaldo, A; Csutor, Z; Klughammer, B; Meng, X; Ciuleanu, T

    2014-11-25

    This phase II, open-label, randomised study evaluated whether patients with metastatic pancreatic cancer receiving erlotinib/gemcitabine derived survival benefits from increasing the erlotinib dose. After a 4-week run-in period (gemcitabine 1000 mg m(-2) once weekly plus erlotinib 100 mg per day), patients with metastatic pancreatic cancer who developed grade 0/1 rash were randomised to receive gemcitabine plus erlotinib dose escalation (150 mg, increasing by 50 mg every 2 weeks (maximum 250 mg); n=71) or gemcitabine plus standard-dose erlotinib (100 mg per day; n=75). The primary end point was to determine whether overall survival (OS) was improved by increasing the erlotinib dose. Secondary end points included progression-free survival (PFS), incidence of grade ⩾2 rash, and safety. Erlotinib dose escalation induced grade ⩾2 rash in 29 out of 71 (41.4%) patients compared with 7 out of 75 (9.3%) patients on standard dose. Efficacy was not significantly different in the dose-escalation arm compared with the standard-dose arm (OS: median 7.0 vs 8.4 months, respectively, hazard ratio (HR), 1.26, 95% confidence interval (CI): 0.88-1.80; P=0.2026; PFS: median 3.5 vs 4.5 months, respectively, HR, 1.09, 95% CI: 0.77-1.54; P=0.6298). Incidence of adverse events was comparable between randomised arms. The erlotinib dose-escalation strategy induced rash in some patients; there was no evidence that the higher dose translated into increased benefit.

  8. Toxic risk of stereotactic body radiotherapy and concurrent helical tomotherapy followed by erlotinib for non-small-cell lung cancer treatment - case report

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    Chen Chien-An

    2010-12-01

    Full Text Available Abstract Background Stereotactic body radiation therapy (SBRT applied by helical tomotherapy (HT is feasible for lung cancer in clinical. Using SBRT concurrently with erlotinib for non-small cell lung cancer (NSCLC is not reported previously. Case Presentation A 77-year-old man with stage III NSCLC, received erlotinib 150 mg/day, combined with image-guided SBRT via HT. A total tumor dose of 54 Gy/9 fractions was delivered to the tumor bed. The tumor responded dramatically and the combined regimen was well tolerated. After concurrent erlotinib-SBRT, erlotinib was continued as maintenance therapy. The patient developed dyspnea three months after the combined therapy and radiation pneumonitis with interstitial lung disease was suspected. Conclusions Combination SBRT, HT, and erlotinib therapy provided effective anti-tumor results. Nonetheless, the potential risks of enhanced adverse effects between radiation and erlotinib should be monitored closely, especially when SBRT is part of the regimen.

  9. Toxic risk of stereotactic body radiotherapy and concurrent helical tomotherapy followed by erlotinib for non-small-cell lung cancer treatment - case report

    International Nuclear Information System (INIS)

    Hsieh, Chen-Hsi; Chen, Chun-Yi; Shueng, Pei-Wei; Chang, Hou-Tai; Lin, Shih-Chiang; Chen, Yu-Jen; Wang, Li-Ying; Hsieh, Yen-Ping; Chen, Chien-An; Chong, Ngot-Swan; Lin, Shoei Long

    2010-01-01

    Stereotactic body radiation therapy (SBRT) applied by helical tomotherapy (HT) is feasible for lung cancer in clinical. Using SBRT concurrently with erlotinib for non-small cell lung cancer (NSCLC) is not reported previously. A 77-year-old man with stage III NSCLC, received erlotinib 150 mg/day, combined with image-guided SBRT via HT. A total tumor dose of 54 Gy/9 fractions was delivered to the tumor bed. The tumor responded dramatically and the combined regimen was well tolerated. After concurrent erlotinib-SBRT, erlotinib was continued as maintenance therapy. The patient developed dyspnea three months after the combined therapy and radiation pneumonitis with interstitial lung disease was suspected. Combination SBRT, HT, and erlotinib therapy provided effective anti-tumor results. Nonetheless, the potential risks of enhanced adverse effects between radiation and erlotinib should be monitored closely, especially when SBRT is part of the regimen

  10. Combination of erlotinib and EGCG induces apoptosis of head and neck cancers through posttranscriptional regulation of Bim and Bcl-2.

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    Haque, Abedul; Rahman, Mohammad Aminur; Chen, Zhuo Georgia; Saba, Nabil F; Khuri, Fadlo R; Shin, Dong M; Ruhul Amin, A R M

    2015-07-01

    Combinatorial approaches using two or more compounds are gaining increasing attention for cancer therapy. We have previously reported that the combination of the EGFR-TKI erlotinib and epigallocatechin-3-gallate (EGCG) exhibited synergistic chemopreventive effects in head and neck cancers by inducing the expression of Bim, p21, p27, and by inhibiting the phosphorylation of ERK and AKT and expression of Bcl-2. In the current study, we further investigated the mechanism of regulation of Bim, Bcl-2, p21 and p27, and their role in apoptosis. shRNA-mediated silencing of Bim significantly inhibited apoptosis induced by the combination of erlotinib and EGCG (p = 0.005). On the other hand, overexpression of Bcl-2 markedly protected cells from apoptosis (p = 0.003), whereas overexpression of constitutively active AKT only minimally protected cells from apoptosis induced by the combination of the two compounds. Analysis of mRNA expression by RT-PCR revealed that erlotinib, EGCG and their combination had no significant effects on the mRNA expression of Bim, p21, p27 or Bcl-2 suggesting the post-transcriptional regulation of these molecules. Furthermore, we found that erlotinib or the combination of EGCG and erlotinib inhibited the phosphorylation of Bim and stabilized Bim after inhibition of protein translation by cycloheximide. Taken together, our results strongly suggest that the combination of erlotinib and EGCG induces apoptosis of SCCHN cells by regulating Bim and Bcl-2 at the posttranscriptional level.

  11. Tyrosine kinase inhibitors show different anti-brain metastases efficacy in NSCLC: A direct comparative analysis of icotinib, gefitinib, and erlotinib in a nude mouse model.

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    Tan, Jianlong; Li, Min; Zhong, Wen; Hu, Chengping; Gu, Qihua; Xie, Yali

    2017-11-17

    Brain metastasis is an increasing problem in non-small cell lung cancer (NSCLC) patients. Tyrosine kinase inhibitors (TKIs), including gefitinib, erlotinib, and icotinib, are reported to be effective in patients with brain metastases. However, direct comparative studies of the pharmacokinetics and efficacy of these three drugs in treating brain metastases are lacking. In the present investigation, we found that gefitinib penetrated the blood-tumor barrier and was distributed to brain metastases more effectively than erlotinib or icotinib in a nude mouse model. The 1-h ratio of brain metastases to plasma concentration for gefitinib, erlotinib, and icotinib was 9.82±1.03%, 4.83±0.25%, and 2.62±0.21%, respectively. The 2-h ratio of brain metastases to plasma concentration for gefitinib, erlotinib, and icotinib was 15.11±2.00%, 5.73±1.31%, and 2.69±0.31%, respectively. Gefitinib exhibited the strongest antitumor activity ( p gefitinib vs. erlotinib =0.005; p gefitinib vs. icotinib =0.002). Notably, erlotinib exhibited a better treatment efficacy than icotinib ( p =0.037). Consistently, immunohistochemical data showed that TKIs differentially inhibit the proliferation of metastatical tumor cells. Gefitinib and erlotinib markedly inhibited the proliferation of tumor cells, while there were more ki-67-positive tumor cells in the icotinib group. Additionally, gefitinib inhibited the phosphorylation of EGFR better than the other drugs, whereas pEGFR expression levels in erlotinib groups were lower than levels in the icotinib group ( p gefitinib vs. erlotinib =0.995; p gefitinib vs. icotinib =0.028; p erlotinib vs. icotinib =0.042).Altogether, our findings suggest that gefitinib and erlotinib can inhibit the growth of PC-9-luc brain tumors. Gefitinib demonstrated better antitumor activity and penetration rate in brain metastases than erlotinib or icotinib.

  12. Preoperative Radiation Therapy With Concurrent Capecitabine, Bevacizumab, and Erlotinib for Rectal Cancer: A Phase 1 Trial

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    Das, Prajnan, E-mail: PrajDas@mdanderson.org [Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Eng, Cathy [Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Rodriguez-Bigas, Miguel A.; Chang, George J.; Skibber, John M.; You, Y. Nancy [Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Maru, Dipen M. [Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Munsell, Mark F. [Department of Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Clemons, Marilyn V. [Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Kopetz, Scott E.; Garrett, Christopher R.; Shureiqi, Imad [Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Delclos, Marc E.; Krishnan, Sunil; Crane, Christopher H. [Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States)

    2014-02-01

    Purpose: The goal of this phase 1 trial was to determine the maximum tolerated dose (MTD) of concurrent capecitabine, bevacizumab, and erlotinib with preoperative radiation therapy for rectal cancer. Methods and Materials: Patients with clinical stage II to III rectal adenocarcinoma, within 12 cm from the anal verge, were treated in 4 escalating dose levels, using the continual reassessment method. Patients received preoperative radiation therapy with concurrent bevacizumab (5 mg/kg intravenously every 2 weeks), erlotinib, and capecitabine. Capecitabine dose was increased from 650 mg/m{sup 2} to 825 mg/m{sup 2} orally twice daily on the days of radiation therapy; erlotinib dose was increased from 50 mg orally daily in weeks 1 to 3, to 50 mg daily in weeks 1 to 6, to 100 mg daily in weeks 1 to 6. Patients underwent surgery at least 9 weeks after the last dose of bevacizumab. Results: A total of 19 patients were enrolled, and 18 patients were considered evaluable. No patient had grade 4 acute toxicity, and 1 patient had grade 3 acute toxicity (hypertension). The MTD was not reached. All 18 evaluable patients underwent surgery, with low anterior resection in 7 (39%), proctectomy with coloanal anastomosis in 4 patients (22%), posterior pelvic exenteration in 1 (6%), and abdominoperineal resection in 6 (33%). Of the 18 patients, 8 (44%) had pathologic complete response, and 1 had complete response of the primary tumor with positive nodes. Three patients (17%) had grade 3 postoperative complications (ileus, small bowel obstruction, and infection). With a median follow-up of 34 months, 1 patient developed distant metastasis, and no patient had local recurrence or died. The 3-year disease-free survival was 94%. Conclusions: The combination of preoperative radiation therapy with concurrent capecitabine, bevacizumab, and erlotinib was well tolerated. The pathologic complete response rate appears promising and may warrant further investigation.

  13. Role of erlotinib in first-line and maintenance treatment of advanced non-small-cell lung cancer

    Directory of Open Access Journals (Sweden)

    Noemí Reguart

    2010-06-01

    Full Text Available Noemí Reguart1, Andrés Felipe Cardona2, Rafael Rosell31Medical Oncology Service, ICMHO, Hospital Clinic Barcelona, Barcelona, Spain; 2Clinical and Translational Oncology Group, Institute of Oncology, Fundación Santa Fe de Bogotá, Bogotá, D.C., Colombia; 3Medical Oncology Service, Catalan Institute of Oncology, ICO, Hospital Germans Trias i Pujol, Badalona, Barcelona, SpainAbstract: Erlotinib hydrochloride (Tarceva® is a member of a class of small molecule inhibitors that targets the tyrosine kinase domain of the epidermal growth factor receptor (EGFR, with anti-tumor activity in preclinical models. Erlotinib represents a new-generation of agents known as “targeted therapies” designed to act upon cancer cells by interfering with aberrant specific activated pathways needed for tumor growth, angiogenesis and cell survival. Since its approval in November 2004 for the treatment of locally advanced or metastatic non-small cell lung cancer (NSCLC after the failure of at least one prior chemotherapy regimen and with a view to improving patients’ outcomes and prevent symptoms, the scientific community has evaluated the potential role of erlotinib in other scenarios such as in maintenance therapy and, in first-line setting for a selected population based on biological markers of response such as mutations of the EGFR. The convenient once-a-day pill administration and the good toxicity profile of erlotinib make it a reasonable candidate for testing in this context. This report provides a review of the role of erlotinib therapy in advanced NSCLC. It summarizes current data and perspectives of erlotinib in upfront treatment and maintenance for advanced NSCLC as well as looking at candidate biomarkers of response to these new targeted-agents.Keywords: erlotinib, tyrosine kinase inhibitors, first line, maintenance, non-small-cell lung cancer

  14. Targeted erlotinib for first-line treatment of advanced non-small cell lung cancer: a budget impact analysis.

    Science.gov (United States)

    Bajaj, Preeti S; Veenstra, David L; Goertz, Hans-Peter; Carlson, Josh J

    2014-08-01

    A recent phase III trial showed that patients with advanced non-small cell lung cancer (NSCLC) whose tumors harbor specific EGFR mutations significantly benefit from first-line treatment with erlotinib compared to chemotherapy. This study sought to estimate the budget impact if coverage for EGFR testing and erlotinib as first-line therapy were provided in a hypothetical 500,000-member managed care plan. The budget impact model was developed from a US health plan perspective to evaluate administration of the EGFR test and treatment with erlotinib for EGFR-positive patients, compared to non-targeted treatment with chemotherapy. The eligible patient population was estimated from age-stratified SEER incidence data. Clinical data were derived from key randomized controlled trials. Costs related to drug, administration, and adverse events were included. Sensitivity analyses were conducted to assess uncertainty. In a plan of 500,000 members, it was estimated there would be 91 newly diagnosed advanced NSCLC patients annually; 11 are expected to be EGFR-positive. Based on the testing and treatment assumptions, it was estimated that 3 patients in Scenario 1 and 6 patients in Scenario 2 receive erlotinib. Overall health plan expenditures would increase by $0.013 per member per month (PMPM). This increase is largely attributable to erlotinib drug costs, in part due to lengthened progression-free survival and treatment periods experienced in erlotinib-treated patients. EGFR testing contributes slightly, whereas adverse event costs mitigate the budget impact. The budget impact did not exceed $0.019 PMPM in sensitivity analyses. Coverage for targeted first-line erlotinib therapy in NSCLC likely results in a small budget impact for US health plans. The estimated impact may vary by plan, or if second-line or maintenance therapy, dose changes/interruptions, or impact on patients' quality-of-life were included.

  15. Radiation recall gastritis secondary to combination of gemcitabine and erlotinib in pancreatic cancer and response to PPI - a case report.

    Science.gov (United States)

    Choi, Seong Ji; Kim, Hyo Jung; Kim, Jae Seon; Bak, Young-Tae; Kim, Jun Suk

    2016-08-02

    Radiation recall gastritis is rare but can be induced after concurrent chemoradiation for pancreatic cancer. We report a patient with pancreatic cancer who developed radiation-recall gastritis related to a combination of gemcitabine and erlotinib. A 54-year-old female with unresectable pancreatic cancer received gemcitabine in combination with radiation therapy followed by chemotherapy with gemcitabine and erlotinib. After completing 2 cycles of chemotherapy, the patient had epigastric pain, nausea, and vomiting. Abdominal computed tomography (CT) scan revealed diffuse wall thickening of the stomach, and esophagogastroduodenoscopy (EGD) showed multiple gastric ulcers. The patient was treated with proton pump inhibitors (PPI) and was continued on maintenance chemotherapy. Two months later, the patient presented with the similar symptoms and persistent gastric ulcers were observed during subsequent EGD. Nevertheless, the patient's symptom had resolved with PPI therapy. Thus, the patient underwent maintenance chemotherapy with gemcitabine and erlotinib for additional 4 cycles. Eventually, follow-up abdominal CT Scan and EGD at 6 months demonstrated resolution of the gastric ulcers. Physicians should be aware of the possibility of radiation recall gastritis associated with a combination of gemcitabine and erlotinib. Administration of PPIs may mitigate the adverse effects of gemcitabine and erlotinib in the presence of radiation recall gastritis; however further studies are warranted.

  16. Radiation recall gastritis secondary to combination of gemcitabine and erlotinib in pancreatic cancer and response to PPI - a case report

    International Nuclear Information System (INIS)

    Choi, Seong Ji; Kim, Hyo Jung; Kim, Jae Seon; Bak, Young-Tae; Kim, Jun Suk

    2016-01-01

    Radiation recall gastritis is rare but can be induced after concurrent chemoradiation for pancreatic cancer. We report a patient with pancreatic cancer who developed radiation-recall gastritis related to a combination of gemcitabine and erlotinib. A 54-year-old female with unresectable pancreatic cancer received gemcitabine in combination with radiation therapy followed by chemotherapy with gemcitabine and erlotinib. After completing 2 cycles of chemotherapy, the patient had epigastric pain, nausea, and vomiting. Abdominal computed tomography (CT) scan revealed diffuse wall thickening of the stomach, and esophagogastroduodenoscopy (EGD) showed multiple gastric ulcers. The patient was treated with proton pump inhibitors (PPI) and was continued on maintenance chemotherapy. Two months later, the patient presented with the similar symptoms and persistent gastric ulcers were observed during subsequent EGD. Nevertheless, the patient’s symptom had resolved with PPI therapy. Thus, the patient underwent maintenance chemotherapy with gemcitabine and erlotinib for additional 4 cycles. Eventually, follow-up abdominal CT Scan and EGD at 6 months demonstrated resolution of the gastric ulcers. Physicians should be aware of the possibility of radiation recall gastritis associated with a combination of gemcitabine and erlotinib. Administration of PPIs may mitigate the adverse effects of gemcitabine and erlotinib in the presence of radiation recall gastritis; however further studies are warranted

  17. The Impact of Smoking Status on the Efficacy of Erlotinib in Patients with Advanced Non-small Cell Lung Cancer

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    Yilong WU

    2009-12-01

    Full Text Available Background and objective Erlotinib is a targeted treatment for advanced non-small cell lung cancer. Smoking status may be one of influencing factors of the efficacy of erlotinib. The aim of this study is to explore the impact of smoking status on the efficacy of erlotinib in patients with advanced non-small cell lung cancer. Methods Patients with nonsmall cell lung cancer who had been previously treated with at least one course of platinum based chemotherapy received 150 mg oral doses of erlotinib once daily until disease progression. Response rate, progression-free survival, overall survival were analyzed in the different smoking status groups. Kaplan-Meier method was used to analyze the survival rate. Results Fortyeight patients were enrolled into the study from December 2005 to September 2006. We followed up these patients until 28th December, 2008. Median follow up time was 30 months. The compliance rate was 100%. The response rate was 32.1% in the smoking group and 35% in the never smoking group (P=0.836; The median progression-free survival was 3 months and 9 months, respectively (P=0.033. The median overall survival was 5 months and 17 months, respectively (P=0.162. Conclusion Erlotinib is an effective drug for advanced non-small cell lung cancer patients with different smoking status. Progressionfree survival is better in the never smoking patients than the smoking patients.

  18. Alterations in Pharmacokinetics of Gemcitabine and Erlotinib by Concurrent Administration of Hyangsayukgunja-Tang, a Gastroprotective Herbal Medicine.

    Science.gov (United States)

    Kim, Tae Hwan; Shin, Soyoung; Kim, Sarah; Bulitta, Jürgen B; Weon, Kwon-Yeon; Joo, Sang Hoon; Ma, Eunsook; Yoo, Sun Dong; Park, Gi-Young; Kwon, Dong Rak; Jeong, Seok Won; Lee, Da Young; Shin, Beom Soo

    2017-09-10

    Gemcitabine and erlotinib are the chemotherapeutic agents used in the treatment of various cancers and their combination is being accepted as a first-line treatment of advanced pancreatic cancer. Hyangsayukgunja-tang (HYT) is a traditional oriental medicine used in various digestive disorders and potentially helpful to treat gastrointestinal adverse effects related to chemotherapy. The present study was aimed to evaluate the effect of HYT on the pharmacokinetics of gemcitabine and erlotinib given simultaneously in rats. Rats were pretreated with HYT at an oral dose of 1200 mg/kg/day once daily for a single day or 14 consecutive days. Immediately after pretreatment with HYT, gemcitabine and erlotinib were administered by intravenous injection (10 mg/kg) and oral administration (20 mg/kg), respectively. The effects of HYT on pharmacokinetics of the two drugs were estimated by non-compartmental analysis and pharmacokinetic modeling. The pharmacokinetics of gemcitabine and erlotinib were not altered by single dose HYT pretreatment. However, the plasma levels of OSI-420 and OSI-413, active metabolites of erlotinib, were significantly decreased in the multiple dose HYT pretreatment group. The pharmacokinetic model estimated increased systemic clearances of OSI-420 and OSI-413 by multiple doses of HYT. These data suggest that HYT may affect the elimination of OSI-420 and OSI-413.

  19. Resistance mechanisms to erlotinib in the non-small cell lung cancer cell line, HCC827 examined by RNA-seq

    DEFF Research Database (Denmark)

    Jacobsen, Kirstine; Alcaraz, Nicolas; Ditzel, Henrik

    (Illumina) prior to sequencing on an Illumina HiSeq platform (100bp paired end). The resistant subclones were examined both in presence and absence of erlotinib. The data was analyzed by an in-house developed pipeline including quality control by Trim Galore v0.3.3, mapping of reads to HG19 by TopHat2 v.2......Background: Erlotinib, an EGFR selective reversible inhibitor, has dramatically changed the treatment of non-small cell lung cancer (NSCLC) as approximately 70% of patients show significant tumor regression upon treatment. However, all patients eventually relapse due to development of acquired...... - in erlotinib-resistant subclones of the NSCLC cell line HCC827. Materials & Methods: We established 3 erlotinib-resistant subclones (resistant to 10, 20, 30 µM erlotinib, respectively), and prepared cDNA libraries of purified RNA from biological duplicates using TruSeq® Stranded Total RNA Ribo-Zero™ Gold...

  20. Phase Ib Study of Lumretuzumab Plus Cetuximab or Erlotinib in Solid Tumor Patients and Evaluation of HER3 and Heregulin as Potential Biomarkers of Clinical Activity

    DEFF Research Database (Denmark)

    Meulendijks, Didier; Jacob, Wolfgang; Voest, Emile E

    2017-01-01

    Purpose: This study investigated the safety, clinical activity, and target-associated biomarkers of lumretuzumab, a humanized, glycoengineered, anti-HER3 monoclonal antibody (mAb), in combination with the EGFR-blocking agents erlotinib or cetuximab in patients with advanced HER3-positive carcinomas.......Experimental Design: The study included two parts: dose escalation and dose extension phases with lumretuzumab in combination with either cetuximab or erlotinib, respectively. In both parts, patients received lumretuzumab doses from 400 to 2,000 mg plus cetuximab or erlotinib according to standard posology......) in the cetuximab part and two DLTs in the erlotinib part were reported. The most frequent adverse events were gastrointestinal and skin toxicities, which were manageable. The objective response rate (ORR) was 6.1% in the cetuximab part and 4.2% in the erlotinib part. In the sqNSCLC extension cohort...

  1. Phase I/II trial of vorinostat (SAHA) and erlotinib for non-small cell lung cancer (NSCLC) patients with epidermal growth factor receptor (EGFR) mutations after erlotinib progression.

    Science.gov (United States)

    Reguart, Noemi; Rosell, Rafael; Cardenal, Felipe; Cardona, Andres F; Isla, Dolores; Palmero, Ramon; Moran, Teresa; Rolfo, Christian; Pallarès, M Cinta; Insa, Amelia; Carcereny, Enric; Majem, Margarita; De Castro, Javier; Queralt, Cristina; Molina, Miguel A; Taron, Miquel

    2014-05-01

    Vorinostat or suberoylanilide hydroxamic acid (SAHA) is a novel histone deacetylase inhibitor with demonstrated antiproliferative effects due to drug-induced accumulation of acetylated proteins, including the heat shock protein 90. We prospectively studied the activity of vorinostat plus erlotinib in EGFR-mutated NSCLC patients with progression to tyrosine kinase inhibitors. We conducted this prospective, non-randomized, multicenter, phase I/II trial to evaluate the maximum tolerated dose, toxicity profile and efficacy of erlotinib and vorinostat. Patients with advanced NSCLC harboring EGFR mutations and progressive disease after a minimum of 12 weeks on erlotinib were included. The maximum tolerated dose of vorinostat plus erlotinib was used as recommended dose for the phase II (RDP2) to assess the efficacy of the combination. The primary end point was progression-free-survival rate at 12 weeks (PFSR12w). Pre-treatment plasma samples were required to assess T790M resistant mutation. A total of 33 patients were enrolled in the phase I-II trial. The maximum tolerated dose was erlotinib 150 mg p.o., QD, and 400mg p.o., QD, on days 1-7 and 15-21 in a 28-day cycle. Among the 25 patients treated at the RDP2, the most common toxicities included anemia, fatigue and diarrhea. No responses were observed. PFSR12w was 28% (IC 95%: 18.0-37.2); median progression-free survival (PFS) was 8 weeks (IC 95%: 7.43-8.45) and overall survival (OS) 10.3 months (95% CI: 2.4-18.1). Full dose of continuous erlotinib with vorinostat 400mg p.o., QD on alternative weeks can be safely administered. Still, the combination has no meaningful activity in EGFR-mutated NSCLC patients after TKI progression. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  2. Plasma and pleural fluid pharmacokinetics of erlotinib and its active metabolite OSI-420 in patients with non-small-cell lung cancer with pleural effusion.

    Science.gov (United States)

    Masago, Katsuhiro; Togashi, Yosuke; Fukudo, Masahide; Terada, Tomohiro; Irisa, Kaoru; Sakamori, Yuichi; Kim, Young Hak; Mio, Tadashi; Inui, Ken-Ichi; Mishima, Michiaki

    2011-09-01

    Erlotinib is orally active and selectively inhibits the tyrosine kinase activity of the epidermal growth factor receptor. The pleural space penetration and exposure of erlotinib is poorly understood. Thus, we investigated the pharmacokinetics (PK) of erlotinib and its active metabolite OSI-420 in non-small-cell lung cancer (NSCLC) of malignant pleural effusion (MPE). We analyzed the PK of erlotinib and OSI-420 on days 1 and 8 after beginning erlotinib therapy in 9 patients with MPE. Their concentrations were determined by high-performance liquid chromatography with ultraviolet detection. Blood samples were obtained five times per day: before administration, and 2, 4, 8, and 24 hours after administration. Pleural effusions were obtained once per day, 2 hours after administration on day 1, and before administration on day 8. The exceptions were cases 2 and 4, which had pleural effusions obtained just before drug administration, and 2, 4, 8, and 24 hours after administration. The mean percentage of penetration from plasma to pleural effusion for erlotinib was 18% on day 1 and 112% on day 8, while these values for OSI-420 were 9.5% on day 1 and 131% on day 8. The area under the drug concentration-time curve of pleural fluid for erlotinib was 28,406 ng-hr/mL for case 2 and 45,906 ng-hr/mL for case 4. There seems to be a significant accumulation of both erlotinib and OSI-420 in MPE with repeated dosing. Although larger studies will be necessary to determine the true impact of erlotinib MPE accumulation on plasma PK and safety, erlotinib can be administered safely to patients with MPE with respect to efficacy and side effects. Copyright © 2011. Published by Elsevier Inc.

  3. Quantitative proteomics identifies central players in erlotinib resistance of the non-small cell lung cancer cell line HCC827

    DEFF Research Database (Denmark)

    Jacobsen, Kirstine; Lund, Rikke Raaen; Beck, Hans Christian

    Background: Erlotinib (Tarceva®, Roche) has significantly changed the treatment of non-small cell lung cancer (NSCLC) as 70% of patients show significant tumor regression when treated. However, all patients relapse due to development of acquired resistance, which in 43-50% of cases are caused...... by a secondary mutation (T790M) in EGFR. Importantly, a majority of resistance cases are still unexplained. Our aim is to identify novel resistance mechanisms in erlotinib-resistant subclones of the NSCLC cell line HCC827. Materials & Methods: We established 3 erlotinib-resistant subclones (resistant to 10, 20...... or other EGFR or KRAS mutations, potentiating the identification of novel resistance mechanisms. We identified 2875 cytoplasmic proteins present in all 4 cell lines. Of these 87, 56 and 23 are upregulated >1.5 fold; and 117, 72 and 32 are downregulated >1.5 fold, respectively, in the 3 resistant clones...

  4. Maintenance erlotinib in advanced nonsmall cell lung cancer: cost-effectiveness in EGFR wild-type across Europe

    Directory of Open Access Journals (Sweden)

    Walleser S

    2012-09-01

    Full Text Available Silke Walleser,1 Joshua Ray,2 Helge Bischoff,3 Alain Vergnenègre,4 Hubertus Rosery,5 Christos Chouaid,6 David Heigener,7 Javier de Castro Carpeño,8 Marcello Tiseo,9 Stefan Walzer21Health Economic Consultancy, Renens, Switzerland; 2F Hoffmann-La Roche Pharmaceuticals AG, Basel, Switzerland; 3Thoracic Hospital of Heidelberg, Heidelberg, Germany; 4Limoges University Hospital, Limoges, France; 5Assessment-in-Medicine GmbH, Loerrach, Germany; 6Hospital Saint Antoine, Paris, France; 7Hospital Grosshansdorf, Grosshansdorf, Germany; 8University Hospital La Paz, Madrid, Spain; 9University Hospital of Parma, Parma, ItalyBackground: First-line maintenance erlotinib in patients with locally advanced or metastatic nonsmall cell lung cancer (NSCLC has demonstrated significant overall survival and progression-free survival benefits compared with best supportive care plus placebo, irrespective of epidermal growth factor receptor (EGFR status (SATURN trial. The cost-effectiveness of first-line maintenance erlotinib in the overall SATURN population has been assessed and published recently, but analyses according to EGFR mutation status have not been performed yet, which was the rationale for assessing the cost-effectiveness of first-line maintenance erlotinib specifically in EGFR wild-type metastatic NSCLC.Methods: The incremental cost per life-year gained of first-line maintenance erlotinib compared with best supportive care in patients with EGFR wild-type stable metastatic NSCLC was assessed for five European countries (the United Kingdom, Germany, France, Spain, and Italy with an area-under-the-curve model consisting of three health states (progression-free survival, progressive disease, death. Log-logistic survival functions were fitted to Phase III patient-level data (SATURN to model progression-free survival and overall survival. The first-line maintenance erlotinib therapy cost (modeled for time to treatment cessation, medication cost in later lines, and

  5. Erlotinib treatment in patients with advanced lung adenocarcinoma with CISH-positive and CISH-negative EGFR gene alterations.

    Science.gov (United States)

    Hou, Ming-Mo; Huang, Shiu-Feng; Kuo, Han-Pin; Yang, Cheng-Ta; Tsai, Ying-Huang; Yu, Chih-Teng; Lin, Horng-Chyuan; Chen, Chih-Hung; Wang, Chih-Liang; Chung, Fu-Tsai; Hsieh, Jia-Juan; Hsu, Todd; Cheng, Hsin-Yi; Ou, Li-Ying; Wang, Hung-Ming; Lin, Yung-Chang; Chang, Nai-Jen; Chang, John Wen-Cheng

    2012-03-01

    Epidermal growth factor receptor (EGFR) positivity as assessed by chromogenic in situ hybridization (CISH) has been demonstrated to be associated with EGFR mutation status. This study was conducted to compare the responsiveness of CISH-positive and CISH-negative lung adenocarcinomas to erlotinib. Patients received erlotinib (150 mg/day) alone until disease progression or intolerable toxicity. EGFR gene status was examined by CISH. The response rate (RR), progression-free survival (PFS), overall survival (OS) and toxicity profiles were assessed. Thirty-one patients underwent response evaluations and CISH analyses, 12 of whom harboured CISH-positive adenocarcinomas. The overall RR (p=0.035), median PFS (p=0.091) and median OS (p=0.408) were higher in the CISH-positive group. No difference in toxicity profiles was observed between these two groups. EGFR status as assessed by CISH can predict the response to erlotinib in patients with advanced lung adenocarcinoma.

  6. EGFR inhibitor erlotinib delays disease progression but does not extend survival in the SOD1 mouse model of ALS.

    Directory of Open Access Journals (Sweden)

    Claire E Le Pichon

    Full Text Available Amyotrophic lateral sclerosis (ALS is a fatal neurodegenerative disease that causes progressive paralysis due to motor neuron death. Several lines of published evidence suggested that inhibition of epidermal growth factor receptor (EGFR signaling might protect neurons from degeneration. To test this hypothesis in vivo, we treated the SOD1 transgenic mouse model of ALS with erlotinib, an EGFR inhibitor clinically approved for oncology indications. Although erlotinib failed to extend ALS mouse survival it did provide a modest but significant delay in the onset of multiple behavioral measures of disease progression. However, given the lack of protection of motor neuron synapses and the lack of survival extension, the small benefits observed after erlotinib treatment appear purely symptomatic, with no modification of disease course.

  7. Phase 2 Study of Erlotinib Combined With Adjuvant Chemoradiation and Chemotherapy in Patients With Resectable Pancreatic Cancer

    International Nuclear Information System (INIS)

    Herman, Joseph M.; Fan, Katherine Y.; Wild, Aaron T.; Hacker-Prietz, Amy; Wood, Laura D.; Blackford, Amanda L.; Ellsworth, Susannah; Zheng, Lei; Le, Dung T.; De Jesus-Acosta, Ana; Hidalgo, Manuel; Donehower, Ross C.; Schulick, Richard D.; Edil, Barish H.; Choti, Michael A.; Hruban, Ralph H.

    2013-01-01

    Purpose: Long-term survival rates for patients with resected pancreatic ductal adenocarcinoma (PDAC) have stagnated at 20% for more than a decade, demonstrating the need to develop novel adjuvant therapies. Gemcitabine-erlotinib therapy has demonstrated a survival benefit for patients with metastatic PDAC. Here we report the first phase 2 study of erlotinib in combination with adjuvant chemoradiation and chemotherapy for resected PDAC. Methods and Materials: Forty-eight patients with resected PDAC received adjuvant erlotinib (100 mg daily) and capecitabine (800 mg/m 2 twice daily Monday-Friday) concurrently with intensity modulated radiation therapy (IMRT), 50.4 Gy over 28 fractions followed by 4 cycles of gemcitabine (1000 mg/m 2 on days 1, 8, and 15 every 28 days) and erlotinib (100 mg daily). The primary endpoint was recurrence-free survival (RFS). Results: The median follow-up time was 18.2 months (interquartile range, 13.8-27.1). Lymph nodes were positive in 85% of patients, and margins were positive in 17%. The median RFS was 15.6 months (95% confidence interval [CI], 13.4-17.9), and the median overall survival (OS) was 24.4 months (95% CI, 18.9-29.7). Multivariate analysis with adjustment for known prognostic factors showed that tumor diameter >3 cm was predictive for inferior RFS (hazard ratio, 4.01; P=.001) and OS (HR, 4.98; P=.02), and the development of dermatitis was associated with improved RFS (HR, 0.27; P=.009). During CRT and post-CRT chemotherapy, the rates of grade 3/4 toxicity were 31%/2% and 35%/8%, respectively. Conclusion: Erlotinib can be safely administered with adjuvant IMRT-based CRT and chemotherapy. The efficacy of this regimen appears comparable to that of existing adjuvant regimens. Radiation Therapy Oncology Group 0848 will ultimately determine whether erlotinib produces a survival benefit in patients with resected pancreatic cancer

  8. Comparison of the inhibition potentials of icotinib and erlotinib against human UDP-glucuronosyltransferase 1A1

    Directory of Open Access Journals (Sweden)

    Xuewei Cheng

    2017-11-01

    Full Text Available UDP-glucuronosyltransferase 1A1 (UGT1A1 plays a key role in detoxification of many potentially harmful compounds and drugs. UGT1A1 inhibition may bring risks of drug–drug interactions (DDIs, hyperbilirubinemia and drug-induced liver injury. This study aimed to investigate and compare the inhibitory effects of icotinib and erlotinib against UGT1A1, as well as to evaluate their potential DDI risks via UGT1A1 inhibition. The results demonstrated that both icotinib and erlotinib are UGT1A1 inhibitors, but the inhibitory effect of icotinib on UGT1A1 is weaker than that of erlotinib. The IC50 values of icotinib and erlotinib against UGT1A1-mediated NCHN-O-glucuronidation in human liver microsomes (HLMs were 5.15 and 0.68 μmol/L, respectively. Inhibition kinetic analyses demonstrated that both icotinib and erlotinib were non-competitive inhibitors against UGT1A1-mediated glucuronidation of NCHN in HLMs, with the Ki values of 8.55 and 1.23 μmol/L, respectively. Furthermore, their potential DDI risks via UGT1A1 inhibition were quantitatively predicted by the ratio of the areas under the concentration–time curve (AUC of NCHN. These findings are helpful for the medicinal chemists to design and develop next generation tyrosine kinase inhibitors with improved safety, as well as to guide reasonable applications of icotinib and erlotinib in clinic, especially for avoiding their potential DDI risks via UGT1A1 inhibition.

  9. Comparison of the inhibition potentials of icotinib and erlotinib against human UDP-glucuronosyltransferase 1A1.

    Science.gov (United States)

    Cheng, Xuewei; Lv, Xia; Qu, Hengyan; Li, Dandan; Hu, Mengmeng; Guo, Wenzhi; Ge, Guangbo; Dong, Ruihua

    2017-11-01

    UDP-glucuronosyltransferase 1A1 (UGT1A1) plays a key role in detoxification of many potentially harmful compounds and drugs. UGT1A1 inhibition may bring risks of drug-drug interactions (DDIs), hyperbilirubinemia and drug-induced liver injury. This study aimed to investigate and compare the inhibitory effects of icotinib and erlotinib against UGT1A1, as well as to evaluate their potential DDI risks via UGT1A1 inhibition. The results demonstrated that both icotinib and erlotinib are UGT1A1 inhibitors, but the inhibitory effect of icotinib on UGT1A1 is weaker than that of erlotinib. The IC 50 values of icotinib and erlotinib against UGT1A1-mediated NCHN- O -glucuronidation in human liver microsomes (HLMs) were 5.15 and 0.68 μmol/L, respectively. Inhibition kinetic analyses demonstrated that both icotinib and erlotinib were non-competitive inhibitors against UGT1A1-mediated glucuronidation of NCHN in HLMs, with the K i values of 8.55 and 1.23 μmol/L, respectively. Furthermore, their potential DDI risks via UGT1A1 inhibition were quantitatively predicted by the ratio of the areas under the concentration-time curve (AUC) of NCHN. These findings are helpful for the medicinal chemists to design and develop next generation tyrosine kinase inhibitors with improved safety, as well as to guide reasonable applications of icotinib and erlotinib in clinic, especially for avoiding their potential DDI risks via UGT1A1 inhibition.

  10. Phase 2 Study of Erlotinib Combined With Adjuvant Chemoradiation and Chemotherapy in Patients With Resectable Pancreatic Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Herman, Joseph M., E-mail: jherma15@jhmi.edu [Department of Radiation Oncology and Molecular Radiation Sciences, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins School of Medicine, Baltimore, Maryland (United States); Fan, Katherine Y.; Wild, Aaron T.; Hacker-Prietz, Amy [Department of Radiation Oncology and Molecular Radiation Sciences, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins School of Medicine, Baltimore, Maryland (United States); Wood, Laura D. [Department of Pathology, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins School of Medicine, Baltimore, Maryland (United States); Blackford, Amanda L. [Department of Oncology Biostatistics, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins School of Medicine, Baltimore, Maryland (United States); Ellsworth, Susannah [Department of Radiation Oncology and Molecular Radiation Sciences, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins School of Medicine, Baltimore, Maryland (United States); Zheng, Lei; Le, Dung T.; De Jesus-Acosta, Ana [Department of Oncology, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins School of Medicine, Baltimore, Maryland (United States); Hidalgo, Manuel [Centro Nacional de Investigaciones Oncologicas, Madrid (Spain); Donehower, Ross C. [Department of Oncology, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins School of Medicine, Baltimore, Maryland (United States); Schulick, Richard D.; Edil, Barish H. [Department of Surgery, University of Colorado Anschutz Medical Campus, Aurora, Colorado (United States); Choti, Michael A. [Department of Surgery, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins School of Medicine, Baltimore, Maryland (United States); Hruban, Ralph H. [Department of Pathology, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins School of Medicine, Baltimore, Maryland (United States); and others

    2013-07-15

    Purpose: Long-term survival rates for patients with resected pancreatic ductal adenocarcinoma (PDAC) have stagnated at 20% for more than a decade, demonstrating the need to develop novel adjuvant therapies. Gemcitabine-erlotinib therapy has demonstrated a survival benefit for patients with metastatic PDAC. Here we report the first phase 2 study of erlotinib in combination with adjuvant chemoradiation and chemotherapy for resected PDAC. Methods and Materials: Forty-eight patients with resected PDAC received adjuvant erlotinib (100 mg daily) and capecitabine (800 mg/m{sup 2} twice daily Monday-Friday) concurrently with intensity modulated radiation therapy (IMRT), 50.4 Gy over 28 fractions followed by 4 cycles of gemcitabine (1000 mg/m{sup 2} on days 1, 8, and 15 every 28 days) and erlotinib (100 mg daily). The primary endpoint was recurrence-free survival (RFS). Results: The median follow-up time was 18.2 months (interquartile range, 13.8-27.1). Lymph nodes were positive in 85% of patients, and margins were positive in 17%. The median RFS was 15.6 months (95% confidence interval [CI], 13.4-17.9), and the median overall survival (OS) was 24.4 months (95% CI, 18.9-29.7). Multivariate analysis with adjustment for known prognostic factors showed that tumor diameter >3 cm was predictive for inferior RFS (hazard ratio, 4.01; P=.001) and OS (HR, 4.98; P=.02), and the development of dermatitis was associated with improved RFS (HR, 0.27; P=.009). During CRT and post-CRT chemotherapy, the rates of grade 3/4 toxicity were 31%/2% and 35%/8%, respectively. Conclusion: Erlotinib can be safely administered with adjuvant IMRT-based CRT and chemotherapy. The efficacy of this regimen appears comparable to that of existing adjuvant regimens. Radiation Therapy Oncology Group 0848 will ultimately determine whether erlotinib produces a survival benefit in patients with resected pancreatic cancer.

  11. Phase II Trial of Erlotinib during and after Radiotherapy in Children with Newly Diagnosed High-Grade Gliomas

    Directory of Open Access Journals (Sweden)

    Ibrahim eQaddoumi

    2014-04-01

    Full Text Available Background. Epidermal growth factor receptor is overexpressed in most pediatric high-grade gliomas (HGG. Since erlotinib had shown activity in adults with HGG, we conducted a phase II trial of erlotinib and local radiotherapy in children with newly diagnosed HGG. Methods. Following maximum surgical resection, patients between 3 and 21 years with nonmetastatic HGG received local radiotherapy at 59.4 Gy (54 Gy for spinal tumors and those with ≥70% brain involvement. Erlotinib started on day 1 of radiotherapy (120 mg/m2 per day and continued for 2 years unless there was tumor progression or intolerable toxicities. The 2-year progression-free survival (PFS was estimated for patients with intracranial anaplastic astrocytoma (AA and glioblastoma.Results. Median age at diagnosis for 41 patients with intracranial tumors (21 with glioblastoma and 20 with AA was 10.9 years (range, 3.3 to 19 years. The 2-year PFS for patients with AA and glioblastoma was 15% ± 7% and 19% ± 8%, respectively. Only five patients remained alive without tumor progression. Twenty-six patients had at least one grade 3 or 4 toxicity irrespective of association with erlotinib; only four required dose modifications. The main toxicities were gastrointestinal (n=11, dermatologic (n=5, and metabolic (n=4. One patient with gliomatosis cerebri who required prolonged corticosteroids died of septic shock associated with pancreatitis. Conclusions. Although therapy with erlotinib was mostly well tolerated, it did not change the poor outcome of our patients. Our results showed that erlotinib is not a promising medication in the treatment of children with intracranial AA and glioblastoma.

  12. Offre pour nos membres

    CERN Multimedia

    Staff Association

    2016-01-01

    Walibi Rhône-Alpes accueille son événement Halloween FreakShow le week-end du 15 et 16 octobre puis tous les jours du 20 octobre au 02 novembre 2016 ! ouverture prolongée jusqu’à 19h et feu d’artifices chaque soir 29, 30 et 31 octobre ! Loup-garou show; 1 labyrinthe; jeu de piste sur le parc (et nombreux lots à gagner); animations (sculpture sur citrouilles et maquillage) et d'autres surpises ! Tarifs pour nos membres : Entrée "Zone terrestre": 23 € au lieu de 29 €. Entrée gratuite pour les enfants de moins de 3 ans, avec accès aux attractions limité. Parking gratuit.

  13. The phosphatase inhibitor menadione (vitamin K3) protects cells from EGFR inhibition by erlotinib and cetuximab.

    Science.gov (United States)

    Perez-Soler, Roman; Zou, Yiyu; Li, Tianhong; Ling, Yi He

    2011-11-01

    Skin toxicity is the main side effect of epidermal growth factor receptor (EGFR) inhibitors, often leading to dose reduction or discontinuation. We hypothesized that phosphatase inhibition in the skin keratinocytes may prevent receptor dephosphorylation caused by EGFR inhibitors and be used as a new potential strategy for the prevention or treatment of this side effect. Menadione (Vitamin K3) was used as the prototype compound to test our hypothesis. HaCat human skin keratinocyte cells and A431 human squamous carcinoma cells were used. EGFR inhibition was measured by Western blotting and immunofluorescence. Phosphatase inhibition and reactive oxygen species (ROS) generation were measured by standard ELISA and fluorescence assays. Menadione caused significant and reversible EGFR activation in a dose-dependent manner starting at nontoxic concentrations. EGFR activation by menadione was associated with reversible protein tyrosine phosphatase inhibition, which seemed to be mediated by ROS generation as exposure to antioxidants prevented both menadione-induced ROS generation and phosphatase inhibition. Short-term coincubation of cells with nontoxic concentrations of menadione and the EGFR inhibitors erlotinib or cetuximab prevented EGFR dephosphorylation. Seventy-two-hour coincubation of cells with the highest nontoxic concentration of menadione and erlotinib provided for a fourfold cell growth inhibitory protection in HaCat human keratinocyte cells. Menadione at nontoxic concentrations causes EGFR activation and prevents EGFR dephosphorylation by erlotinib and cetuximab. This effect seems to be mediated by ROS generation and secondary phosphatase inhibition. Mild oxidative stress in skin keratinocytes by topical menadione may protect the skin from the toxicity secondary to EGFR inhibitors without causing cytotoxicity. ©2011 AACR

  14. Phase II trial of sorafenib and erlotinib in advanced pancreatic cancer

    International Nuclear Information System (INIS)

    Cardin, Dana B; Goff, Laura; Li, Chung-I; Shyr, Yu; Winkler, Charles; DeVore, Russell; Schlabach, Larry; Holloway, Melanie; McClanahan, Pam; Meyer, Krista; Grigorieva, Julia; Berlin, Jordan; Chan, Emily

    2014-01-01

    This trial was designed to assess efficacy and safety of erlotinib with sorafenib in the treatment of patients with advanced pancreatic adenocarcinoma. An exploratory correlative study analyzing pretreatment serum samples using a multivariate protein mass spectrometry-based test (VeriStrat®), previously shown to correlate with outcomes in lung cancer patients treated with erlotinib, was performed. Patients received sorafenib 400 mg daily along with erlotinib 150 mg daily with a primary endpoint of 8-week progression free survival (PFS) rate. Pretreatment serum sample analysis by VeriStrat was done blinded to clinical and outcome data; the endpoints were PFS and overall survival (OS). Difference between groups (by VeriStrat classification) was assessed using log-rank P values; hazard ratios (HR) were obtained from Cox proportional hazards model. Thirty-six patients received study drug and were included in the survival analysis. Eight-week PFS rate of 46% (95% confidence interval (CI): 0.32–0.67) did not meet the primary endpoint of a rate ≥70%. Thirty-two patients were included in the correlative analysis, and VeriStrat “Good” patients had superior PFS (HR = 0.18, 95% CI: 0.06–0.57; P = 0.001) and OS (HR = 0.31 95% CI: 0.13–0.77, P = 0.008) compared to VeriStrat “Poor” patients. Grade 3 toxicities of this regimen included fever, anemia, diarrhea, dehydration, rash, and altered liver function. This study did not meet the primary endpoint, and this combination will not be further pursued. In this small retrospective analysis, the proteomic classification was significantly associated with clinical outcomes and is being further evaluated in ongoing studies

  15. Sequentially administrated of pemetrexed with icotinib/erlotinib in lung adenocarcinoma cell lines in vitro

    OpenAIRE

    Feng, Xiuli; Zhang, Yan; Li, Tao; Li, Yu

    2017-01-01

    Combination of chemotherapy and epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) had been proved to be a potent anti-drug for the treatment of tumors. However, survival time was not extended for the patients with lung adenocarcinoma (AdC) compared with first-line chemotherapy. In the present study, we attempt to assess the optimal schedule of the combined administration of pemetrexed and icotinib/erlotinib in AdC cell lines. Human lung AdC cell lines with wild-type (A54...

  16. Safety and pharmacokinetics of motesanib in combination with gemcitabine and erlotinib for the treatment of solid tumors: a phase 1b study

    Directory of Open Access Journals (Sweden)

    Sun Yu-Nien

    2011-07-01

    Full Text Available Abstract Background This phase 1b study assessed the maximum tolerated dose (MTD, safety, and pharmacokinetics of motesanib (a small-molecule antagonist of VEGF receptors 1, 2, and 3; platelet-derived growth factor receptor; and Kit administered once daily (QD or twice daily (BID in combination with erlotinib and gemcitabine in patients with solid tumors. Methods Patients received weekly intravenous gemcitabine (1000 mg/m2 and erlotinib (100 mg QD alone (control cohort or in combination with motesanib (50 mg QD, 75 mg BID, 125 mg QD, or 100 mg QD; cohorts 1-4; or erlotinib (150 mg QD in combination with motesanib (100 or 125 mg QD; cohorts 5 and 6. Results Fifty-six patients were enrolled and received protocol-specified treatment. Dose-limiting toxicities occurred in 11 patients in cohorts 1 (n = 2, 2 (n = 4, 3 (n = 3, and 6 (n = 2. The MTD of motesanib in combination with gemcitabine and erlotinib was 100 mg QD. Motesanib 125 mg QD was tolerable only in combination with erlotinib alone. Frequently occurring motesanib-related adverse events included diarrhea (n = 19, nausea (n = 18, vomiting (n = 13, and fatigue (n = 12, which were mostly of worst grade Conclusions Treatment with motesanib 100 mg QD plus erlotinib and gemcitabine was tolerable. Motesanib 125 mg QD was tolerable only in combination with erlotinib alone. Trial Registration ClinicalTrials.gov NCT01235416

  17. Phase I Study of Concurrent Whole Brain Radiotherapy and Erlotinib for Multiple Brain Metastases From Non-Small-Cell Lung Cancer

    International Nuclear Information System (INIS)

    Lind, Joline S.W.; Lagerwaard, Frank J.; Smit, Egbert F.; Senan, Suresh

    2009-01-01

    Purpose: Erlotinib has shown activity in patients with brain metastases from non-small-cell lung cancer. The present dose-escalation Phase I trial evaluated the toxicity of whole brain radiotherapy (WBRT) with concurrent and maintenance erlotinib in this patient group. Methods and Materials: Erlotinib (Cohort 1, 100 mg/d; Cohort 2, 150 mg/d) was started 1 week before, and continued during, WBRT (30 Gy in 10 fractions). Maintenance erlotinib (150 mg/d) was continued until unacceptable toxicity or disease progression. Results: A total of 11 patients completed WBRT, 4 in Cohort 1 and 7 in Cohort 2. The median duration of erlotinib treatment was 83 days. No treatment-related neurotoxicity was observed. No treatment-related Grade 3 or greater toxicity occurred in Cohort 1. In Cohort 2, 1 patient developed a Grade 3 acneiform rash and 1 patient had Grade 3 fatigue. Two patients in Cohort 2 developed erlotinib-related interstitial lung disease, contributing to death during maintenance therapy. The median overall survival and interval to progression was 133 and 141 days, respectively. Six patients developed extracranial progression; only 1 patient had intracranial progression. In 7 patients with follow-up neuroimaging at 3 months, 5 had a partial response and 2 had stable disease. Conclusion: WBRT with concurrent erlotinib is well tolerated in patients with brain metastases from non-small-cell lung cancer. The suggestion of a high intracranial disease control rate warrants additional study.

  18. Our Experiences with Erlotinib in Second and Third Line Treatment Patients with Advanced Stage Iiib/ Iv Non-Small Cell Lung Cancer

    Directory of Open Access Journals (Sweden)

    Bakir Mehić

    2008-11-01

    Full Text Available HeadHER1/EGFR is known to play a pivotal role in tumorigenesis and is overexpressed in up to 80% of NSCLCs. The study of an Expanded Access Clinical Program of Erlotinib in NSCLC is a phase IV openlabel, non-randomized, multicenter trial in patients with advanced (inoperable stage IIIb/IV NSCLC who were eligible for treatment with erlotinib but had no access to trial participation. Patients for the study from Bosnia and Herzegovina (B&H were selected from two Clinical centres (Sarajevo and Banja Luka. The aim of study was to evaluated efficacy and tolerability of erlotinib monotherapy in this setting. All patients who received at least one dose of erlotinib and data were entered in the database as of the CRF cut-off date of 14th May 2008 were included in analysis of data (n = 19. This population is defined as the Intent to Treat (ITT population and includes all patients who had at least one dose of erlotinib regardless of whether major protocol violations were incurred. The findings are consistent with the results of the randomized, placebo-controlled BR.21 study. Indicating that erlotinib is an effective option for patients with advanced NSCLC who are unsuitable for, or who have previously failed standard chemotherapy. In B&H group of patients DCR was almost 84%, and PFS was approximately 24,7 weeks (compared with 44% and 9,7 weeks for erlotinib reported in phase III. Almost three quarter of the patients received erlotinib as their second line of therapy. Overall, erlotinib was well tolerated; there were no patients who withdrew due to a treatment-related AE (mainly rash and there were few dose reductions. 24% of patients experienced an SAE (most commonly gastrointestinal (GI disorders.

  19. Phase 2 Study of Bevacizumab Plus Erlotinib in Patients With Advanced Hepatocellular Cancer

    Science.gov (United States)

    Philip, Philip A.; Mahoney, Michelle R.; Holen, Kyle D.; Northfelt, Donald W.; Pitot, Henry C.; Picus, Joel; Flynn, Patrick J.; Erlichman, Charles

    2013-01-01

    BACKGROUND Epidermal growth factor receptor (EGFR) and vascular endothelial growth factor (VEGF) are rational targets for therapy in hepatocellular cancer (HCC). METHODS Patients with histologically proven HCC and not amenable to curative or liver directed therapy were included in this 2-stage phase 2 trial. Eligibility included an Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 or 1 and Child’s Pugh score of A or B, and 1 prior systemic therapy. Patients received erlotinib 150 mg daily and bevacizumab 10 mg/kg on days 1 and 15 every 28 days. Objective tumor response was the primary end point. RESULTS Twenty-seven patients with advanced HCC (median age, 60 years) were enrolled in this multi-institutional study. The proportion of patients with Child’s A classification was 74%. One patient had a confirmed partial response and 11 (48%) achieved stable disease. Median time to disease progression was 3.0 months (95% confidence interval [CI], 1.8-7.1). Median survival time was 9.5 months (95% CI, 7.1-17.1). Grade 3 toxicities included rash, hypertension, fatigue, and diarrhea. CONCLUSIONS In this trial, erlotinib combined with bevacizumab had minimal activity in patients with advanced HCC based on objective response and progression-free survival. The role of targeting EGFR and VEGF in HCC needs further evaluation in molecularly selected patients. PMID:21953248

  20. A randomized phase II trial of first-line treatment with gemcitabine, erlotinib, or gemcitabine and erlotinib in elderly patients (age ≥70 years) with stage IIIB/IV non-small cell lung cancer.

    Science.gov (United States)

    Stinchcombe, Thomas E; Peterman, Amy H; Lee, Carrie B; Moore, Dominic T; Beaumont, Jennifer L; Bradford, Daniel S; Bakri, Kamal; Taylor, Mark; Crane, Jeffrey M; Schwartz, Garry; Hensing, Thomas A; McElroy, Edwin; Niell, Harvey B; Harper, Harry D; Pal, Sridhar; Socinski, Mark A

    2011-09-01

    Single-agent gemcitabine is a standard of care for elderly patients with advanced non-small cell lung cancer, but novel therapies are needed for this patient population. We performed a noncomparative randomized phase II trial of gemcitabine, erlotinib, or the combination in elderly patients (age ≥70 years) with stage IIIB or IV non-small cell lung cancer. Patients were randomized to arms: A (gemcitabine 1200 mg/m on days 1 and 8 every 21 days), B (erlotinib 150 mg daily), or C (gemcitabine 1000 mg/m on days 1 and 8 every 21 days and erlotinib 100 mg daily). Arms B and C were considered investigational; the primary objective was 6-month progression-free survival. Between March 2006 and May 2010, 146 eligible patients received protocol therapy. The majority of the patients (82%) had stage IV disease, 64% reported adenocarcinoma histology, 90% reported current or previous tobacco use, and 28% had a performance status of 2. The 6-month progression-free survival rate observed in arms A, B, and C was 22% (95% confidence interval [CI] 11-35), 24% (95% CI 13-36), and 25% (95% CI 15-38), respectively; the median overall survival observed was 6.8 months (95% CI 4.8-8.5), 5.8 months (95% CI 3.0-8.3), and 5.6 months (95% CI 3.5-8.4), respectively. The rate of grade ≥3 hematological and nonhematological toxicity observed was similar in all three arms. The best overall health-related quality of life response did not differ between treatment arms. Erlotinib or erlotinib and gemcitabine do not warrant further investigation in an unselected elderly patient population.

  1. Comparison of erlotinib and pemetrexed as second-/third-line treatment for lung adenocarcinoma patients with asymptomatic brain metastases

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    He YY

    2016-04-01

    Full Text Available Yayi He,1,* Wenwen Sun,2,* Yan Wang,3,* Shengxiang Ren,1 Xuefei Li,3 Jiayu Li,3 Christopher J Rivard,4 Caicun Zhou,1 Fred R Hirsch4 1Department of Oncology, Shanghai Pulmonary Hospital, 2Clinic and Research Center of Tuberculosis, Shanghai Key Laboratory of Tuberculosis, Shanghai Pulmonary Hospital, 3Department of Lung Cancer and Immunology, Shanghai Pulmonary Hospital, Tongji University Medical School Cancer Institute, Tongji University School of Medicine, Shanghai, People’s Republic of China; 4Division of Medical Oncology, Department of Medicine, University of Colorado, Aurora, CO, USA *These authors contributed equally to this work Objective: Brain metastases occur in one-third of all non-small-cell lung cancer patients. Due to restrictive transport at the blood–brain barrier, many drugs provide poor control of metastases in the brain. The aim of this study was to compare erlotinib with pemetrexed as second-/third-line treatment in patients with lung adenocarcinoma with asymptomatic brain metastases.Methods: From January 2012 to June 2014, all lung adenocarcinoma patients with asymptomatic brain metastases who received treatment with erlotinib or pemetrexed as second-/third-line treatment were retrospectively reviewed. Chi-square and log-rank tests were used to perform statistical analysis.Results: The study enrolled 99 patients, of which 44 were positive for EGFR mutation. Median progression-free survival (PFS in months was not significantly different between the erlotinib- and pemetrexed-treated groups (4.2 vs 3.4 months; 95% confidence interval [CI]: 2.01–6.40 vs 2.80–5.00, respectively; P=0.635. Median PFS was found to be significantly longer in EGFR mutation–positive patients in the erlotinib-treated group (8.0 months; 95% CI 5.85–10.15 compared to the pemetrexed group (3.9 months; 95% CI: 1.25–6.55; P=0.032. The most common treatment-related side effect was mild-to-moderate rash and the most common drug-related side

  2. Informatique: tous pour un ... projet

    CERN Multimedia

    Delétraz, F; Requin, J-M

    2004-01-01

    "Pour des raisons de coût et d'efficacité, les chercheurs font de plus en plus travailler ensemble des ordinateurs éparpillés sur tous les continents. Pour faire avancer la science, tous les moyens et tous les réseaux sont bons" (1 page)

  3. Erlotinib in the Second/Third Line Treatment of Patients with Advanced Non-small Cell Lung Cancer

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    Yilong WU

    2009-05-01

    Full Text Available Background and objective Erlotinib is a targeted drug for non-small cell lung cancer (NSCLC. The aim of this study is to evaluate the efficacy, influencing factors and toxicity of erlotinib in patients with NSCLC. Methods Patients with NSCLC who had been previously treated with at least one course of platinum based chemotherapyreceived 150 mg oral doses of erlotinib once daily until disease progression. Response rate, progression free survival, overall survival and toxicity profile were analyzed. Kaplan-Meier methods was used to analyze the survival rate. Cox regression was used to define the predictive factors. Results Forty-eight patients were enrolled into the study from Dec, 2005 to Sep, 2006. We followed up these patients until 08.Dec.2008. Median follow up time was 30 months. The compliance rate was 100%. The median symptom improving time was 7 days. Partial response 33.4% (16/48, stable disease 22.9% (11/48, and progressive disease 43.7% (21/48. Response rate was 33.4% (16/48. Disease control rate was 56.3% (27/48. One and two-year progression-free survival rates and overall survival rates were 25%(events 36, 8.3% (events 40 and 43.8% (death 27, 20.8% (death 38; three-year overall survival 5.6%. The median progression-free survival time and median overall survival time was 5 months and 8 months, respectively. Performance status was the only predictor for overall survival in the Cox model (P <0.001. Skin toxicity(grade 1 to 3 was found in 93.7% patients. One patient discontinued erlotinib because of perianal abscess. Conclusion Erlotinib is another effective drug for patients with previously chemotherapy advanced NSCLC and accepted toxicity profile.

  4. Identification of resistance mechanisms in erlotinib-resistant subclones of the non-small cell lung cancer cell line HCC827 by exome sequencing

    DEFF Research Database (Denmark)

    Jacobsen, Kirstine; Alcaraz, Nicolas; Lund, Rikke Raaen

    the SeqCap EZ Human Exome Library v3.0 kit and whole-exome sequencing of these (100 bp paired-end) were performed on an Illumina HiSeq 2000 platform. Using a recently developed in-house analysis pipeline the sequencing data were analyzed. The analysis pipeline includes quality control using Trim......Background: Erlotinib (Tarceva®, Roche) has significantly changed the treatment of non-small cell lung cancer (NSCLC) as 70% of patients show significant tumor regression upon treatment (Santarpia et. al., 2013). However, all patients relapse due to development of acquired resistance, which...... mutations in erlotinib-resistant subclones of the NSCLC cell line, HCC827. Materials & Methods: We established 3 erlotinib-resistant subclones (resistant to 10, 20, 30 µM erlotinib, respectively). DNA libraries of each subclone and the parental HCC827 cell line were prepared in biological duplicates using...

  5. Antitumor activity of erlotinib (OSI-774, Tarceva) alone or in combination in human non-small cell lung cancer tumor xenograft models.

    Science.gov (United States)

    Higgins, Brian; Kolinsky, Kenneth; Smith, Melissa; Beck, Gordon; Rashed, Mohammad; Adames, Violeta; Linn, Michael; Wheeldon, Eric; Gand, Laurent; Birnboeck, Herbert; Hoffmann, Gerhard

    2004-06-01

    Our objective was the preclinical assessment of the pharmacokinetics, monotherapy and combined antitumor activity of the epidermal growth factor receptor (HER1/EGFR) tyrosine kinase inhibitor erlotinib in athymic nude mice bearing non-small cell lung cancer (NSCLC) xenograft models. Immunohistochemistry determined the HER1/EGFR status of the NSCLC tumor models. Pharmacokinetic studies assessed plasma drug concentrations of erlotinib in tumor- and non-tumor-bearing athymic nude mice. These were followed by maximum tolerated dose (MTD) studies for erlotinib and each chemotherapy. Erlotinib was then assessed alone and in combination with these chemotherapies in the NSCLC xenograft models. Complete necropsies were performed on most of the animals in each study to further assess antitumor or toxic effects. Erlotinib monotherapy dose-dependently inhibited tumor growth in the H460a tumor model, correlating with circulating levels of drug. There was antitumor activity at the MTD with each agent tested in both the H460a and A549 tumor models (erlotinib 100 mg/kg: 71 and 93% tumor growth inhibition; gemcitabine 120 mg/kg: 93 and 75% tumor growth inhibition; cisplatin 6 mg/kg: 81 and 88% tumor growth inhibition). When each compound was given at a fraction of the MTD, tumor growth inhibition was suboptimal. Combinations of gemcitabine or cisplatin with erlotinib were assessed at 25% of the MTD to determine efficacy. In both NSCLC models, doses of gemcitabine (30 mg/kg) or cisplatin (1.5 mg/kg) with erlotinib (25 mg/kg) at 25% of the MTD were well tolerated. For the slow growing A549 tumor, there was significant tumor growth inhibition in the gemcitabine/erlotinib and cisplatin/erlotinib combinations (above 100 and 98%, respectively), with partial regressions. For the faster growing H460a tumor, there was significant but less remarkable tumor growth inhibition in these same combinations (86 and 53% respectively). These results show that in NSCLC xenograft tumors with similar

  6. Radiosynthesis and biological evaluation of 18F-labeled 4-anilinoquinazoline derivative (18F-FEA-Erlotinib) as a potential EGFR PET agent.

    Science.gov (United States)

    Huang, Shun; Han, Yanjiang; Chen, Min; Hu, Kongzhen; Qi, Yongshuai; Sun, Penghui; Wang, Men; Wu, Hubing; Li, Guiping; Wang, Quanshi; Du, Zhiyun; Zhang, Kun; Zhao, Suqing; Zheng, Xi

    2018-04-01

    Epidermal growth factor receptor (EGFR) has gained significant attention as a therapeutic target. Several EGFR targeting drugs (Gefitinib and Erlotinib) have been approved by US Food and Drug Administration (FDA) and have received high approval in clinical treatment. Nevertheless, the curative effect of these medicines varied in many solid tumors because of the different levels of expression and mutations of EGFR. Therefore, several PET radiotracers have been developed for the selective treatment of responsive patients who undergo PET/CT imaging for tyrosine kinase inhibitor (TKI) therapy. In this study, a novel fluorine-18 labeled 4-anilinoquinazoline based PET tracer, 1N-(3-(1-(2- 18 F-fluoroethyl)-1H-1,2,3-triazol-4-yl)phenyl)-6,7-bis(2-methoxyethoxy)quinazolin-4-amine ( 18 F-FEA-Erlotinib), was synthesized and biological evaluation was performed in vitro and in vivo. 18 F-FEA-Erlotinib was achieved within 50min with over 88% radiochemical yield (decay corrected RCY), an average specific activity over 50GBq/μmol, and over 99% radiochemical purity. In vitro stability study showed no decomposition of 18 F-FEA-Erlotinib after incubated in PBS and FBS for 2h. Cellular uptake and efflux experiment results indicated the specific binding of 18 F-FEA-Erlotinib to HCC827 cell line with EGFR exon 19 deletions. In vivo, Biodistribution studies revealed that 18 F-FEA-Erlotinib exhibited rapid blood clearance both through hepatobiliary and renal excretion. The tumor uptake of 18 F-FEA-Erlotinib in HepG2, HCC827, and A431 tumor xenografts, with different EGFR expression and mutations, was visualized in PET images. Our results demonstrate the feasibility of using 18 F-FEA-Erlotinib as a PET tracer for screening EGFR TKIs sensitive patients. Copyright © 2017 Elsevier Ltd. All rights reserved.

  7. Dramatic response to high-dose icotinib in a lung adenocarcinoma patient after erlotinib failure.

    Science.gov (United States)

    Guan, Yin; Zhao, Hong; Meng, Jing; Yan, Xiang; Jiao, ShunChang

    2014-02-01

    Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) retreatment is rarely administered for non-small cell lung cancer (NSCLC) patients who did not respond to previous TKI treatment. A high dose of TKI may overcome resistance to the standard dose of TKI and have different effectiveness toward cancer compared with the standard dose of TKI. This manuscript describes a dramatic and durable response to high-dose icotinib in a NSCLC patient who did not respond to a previous standard dose of erlotinib. The treatment extended the life of the patient for one additional year. A higher dose of icotinib deserves further study not only for patients whose therapy failed with the standard dose of TKI but also for newly diagnosed NSCLC patients with a sensitive mutation. Serial mutation testing during disease development is necessary for analysis and evaluation of EGFR TKI treatment. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

  8. Population pharmacokinetics/pharmacodynamics of erlotinib and pharmacogenomic analysis of plasma and cerebrospinal fluid drug concentrations in Japanese patients with non-small cell lung cancer.

    Science.gov (United States)

    Fukudo, Masahide; Ikemi, Yasuaki; Togashi, Yosuke; Masago, Katsuhiro; Kim, Young Hak; Mio, Tadashi; Terada, Tomohiro; Teramukai, Satoshi; Mishima, Michiaki; Inui, Ken-Ichi; Katsura, Toshiya

    2013-07-01

    Erlotinib shows large inter-patient pharmacokinetic variability, but the impact of early drug exposure and genetic variations on the clinical outcomes of erlotinib remains fully investigated. The primary objective of this study was to clarify the population pharmacokinetics/pharmacodynamics of erlotinib in Japanese patients with non-small cell lung cancer (NSCLC). The secondary objective was to identify genetic determinant(s) for the cerebrospinal fluid (CSF) permeability of erlotinib and its active metabolite OSI-420. A total of 88 patients treated with erlotinib (150 mg/day) were enrolled, and CSF samples were available from 23 of these patients with leptomeningeal metastases. Plasma and CSF concentrations of erlotinib and OSI-420 were measured by high-performance liquid chromatography with UV detection. Population pharmacokinetic analysis was performed with the nonlinear mixed-effects modelling program NONMEM. Germline mutations including ABCB1 (1236C>T, 2677G>T/A, 3435C>T), ABCG2 (421C>A), and CYP3A5 (6986A>G) polymorphisms, as well as somatic EGFR activating mutations if available, were examined. Early exposure to erlotinib and its safety/efficacy relationship were evaluated. The apparent clearance of erlotinib and OSI-420 were significantly decreased by 24 and 35 % in patients with the ABCG2 421A allele, respectively (p OSI-420 (p model showed that erlotinib trough (C0) levels on day 8 were an independent risk factor for the development of grade ≥2 diarrhea (p = 0.037) and skin rash (p = 0.031). Interstitial lung disease (ILD)-like events occurred in 3 patients (3.4 %), and the median value of erlotinib C0 levels adjacent to these events was approximately 3 times higher than that in patients who did not develop ILD (3253 versus 1107 ng/mL; p = 0.014). The objective response rate in the EGFR wild-type group was marginally higher in patients achieving higher erlotinib C0 levels (≥1711 ng/mL) than that in patients having lower erlotinib C0

  9. Docetaxel-carboplatin in combination with erlotinib and/or bevacizumab in patients with non-small cell lung cancer

    Directory of Open Access Journals (Sweden)

    Boutsikou E

    2013-03-01

    Full Text Available Eftimia Boutsikou,1 Theodoros Kontakiotis,1 Paul Zarogoulidis,1 Kaid Darwiche,2 Ellada Eleptheriadou,1 Konstantinos Porpodis,1 Grammati Galaktidou,3 Leonidas Sakkas,4 Wolfgang Hohenforst-Schmidt,5 Kosmas Tsakiridis,6 Theodoros Karaiskos,7 Konstantinos Zarogoulidis11Pulmonary Department-Oncology Unit, G Papanikolaou General Hospital, Aristotle University of Thessaloniki, Greece; 2University Pulmonary Department-Interventional Unit, Ruhrland Klinic, University of Duisburg-Essen, Essen, Germany; 3Theagenio Anticancer Institute Research Laboratory, 4Department of Pathology, G Papanikolaou Hospital, Thessaloniki, Greece; 5II Medical Clinic, Hospital Coburg, University of Wuerzburg, Coburg, Germany; 6Cardiothoracic Surgery Department, Saint Luke Private Hospital, Panorama, 7Cardiothoracic Surgery Department, G Papanikolaou General Hospital, Aristotle University of Thessaloniki, Thessaloniki, GreeceBackground: Bevacizumab and erlotinib have been demonstrated to prolong overall survival in patients with non-squamous non-small cell lung cancer (NSCLC. We designed a four-arm Phase III trial to evaluate the efficacy and toxicity of the combination of docetaxel, carboplatin, bevacizumab, and erlotinib in the first-line treatment of patients with NSCLC.Methods: A total of 229 patients with stage IIIb/IV non-squamous NSCLC were treated with two cycles of carboplatin (area under the concentration-time curve 5.5 and docetaxel 100 mg/m2 as chemotherapy. After completion of two treatment cycles, patients were evaluated for response and divided into four groups: 61/229 continued with four more cycles of chemotherapy (control group, 52/229 received chemotherapy plus erlotinib 150 mg daily, 56/229 received chemotherapy plus bevacizumab 7.5 mg/kg, and 60/229 were treated with the combination of chemotherapy, erlotinib, and bevacizumab until disease progression. The primary endpoint was overall survival.Results: Over 4 years of follow-up, there was no statistically

  10. Long-term treatment with EGFR inhibitor erlotinib attenuates renal inflammatory cytokines but not nephropathy in Alport syndrome mouse model.

    Science.gov (United States)

    Omachi, Kohei; Miyakita, Rui; Fukuda, Ryosuke; Kai, Yukari; Suico, Mary Ann; Yokota, Tsubasa; Kamura, Misato; Shuto, Tsuyoshi; Kai, Hirofumi

    2017-12-01

    Alport syndrome (AS) is a hereditary kidney disease caused by mutation of type IV collagen. Loss of collagen network induces collapse of glomerular basement membrane (GBM) structure. The previous studies showed that upregulation of some tyrosine kinase receptors signaling accompanied GBM disorder in AS mouse model. EGFR signaling is one of the well-known receptor kinase signaling that is involved in glomerular diseases. However, whether EGFR signaling is relevant to AS progression is still uninvestigated. Here, we determined the involvement of EGFR in AS and the effect of suppressing EGFR signaling by erlotinib treatment on AS progression. Phosphorylated EGFR expression was investigated by Western blotting analysis and immunostaining of kidney tissues of Col4a5 mutant mice (a mouse model of X-linked AS). To check the effect of blocking EGFR signaling in AS, we administered erlotinib to AS mice once a day (10 mg/kg/day) orally for 18 weeks. Renal function parameters (proteinuria, serum creatinine, and BUN) and renal histology were assessed, and the gene expressions of inflammatory cytokines were analyzed in renal tissues. Phosphorylated EGFR expression was upregulated in AS mice kidney tissues. Erlotinib slightly reduced the urinary protein and suppressed the expression of renal injury markers (Lcn2, Lysozyme) and inflammatory cytokines (Il-6, Il-1β and KC). Erlotinib did not improve renal pathology, such as glomerular sclerosis and fibrosis. These findings suggest that EGFR signaling is upregulated in kidney, but although inhibiting this signaling pathway suppressed renal inflammatory cytokines, it did not ameliorate renal dysfunction in AS mouse model.

  11. Sustained Complete Response after Maintenance Therapy with Topotecan and Erlotinib for Recurrent Cervical Cancer with Distant Metastases

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    Donato Callegaro-Filho

    2014-01-01

    Full Text Available Introduction: Recurrent cervical cancer is associated with a poor prognosis. Most treatment responses are partial and of short duration. The development of new therapies is vital to improve treatment for recurrent disease. Epidermal growth factor receptor (EGFR inhibitors may have a role in this setting. Case Description: A 53-year-old woman with stage IB2 squamous cell carcinoma of the cervix was initially treated with chemoradiation. Six months after completing treatment, she developed a recurrence in the common iliac and para-aortic lymph nodes above the previous radiation field and was treated with additional radiation therapy. Two years later, she developed recurrent disease in the left supraclavicular lymph nodes and was treated with chemoradiation followed by 3 cycles of adjuvant cisplatin and topotecan. She had a complete response and was placed on maintenance therapy with topotecan and erlotinib, which was well tolerated and produced minimal side effects. After 20 months of maintenance therapy, it was discontinued given the long interval without evidence of disease. The patient is currently without evidence of disease 5 years after completing the topotecan-erlotinib treatment. Conclusion: We noted a sustained response in a patient with recurrent metastatic cervical cancer treated with radiotherapy, cisplatin, and topotecan followed by maintenance therapy with topotecan and erlotinib. Further evaluation of the role of EGFR inhibitors in this setting should be considered given their favorable toxicity profile and biological relevance.

  12. The role of BIM-EL and BCL2-α on the efficacy of erlotinib and gefitinib in lung cancer.

    Science.gov (United States)

    Simasi, Jacinta; Oelkrug, Christopher; Schubert, Andreas; Nieber, Karen; Gillissen, Adrian

    2015-04-01

    Tyrosine kinase inhibitors (TKI), erlotinib and gefitinib are small molecule inhibitors which are used for the treatment of lung cancer. But, the development of drug resistance has been reported as one of the major setbacks in oncology. This study focused on the mechanisms leading to secondary resistance by assessing the gene expression of BCL2 family proteins which are associated with the intrinsic apoptotic signaling pathway. 8 genes were investigated in erlotinib and gefitinib treated cells by real time PCR and protein analysis by western blotting. The cells were exposed to the test drugs 48h prior to RNA or protein isolation. It was observed that BIM-EL, a pro-apoptotic protein was up-regulated in cells sensitive to the drugs but not in the resistant cells. On the other hand BCL2-α, an anti-apoptotic protein was up-regulated in the resistant cells and not in the sensitive cells. BCL2-α revealed a counter-regulation effect on BIM-EL and this effect is probably one of the causes of secondary resistance to erlotinib and gefitinib. Copyright © 2014 Elsevier B.V. All rights reserved.

  13. Phase I evaluation of intravenous ascorbic acid in combination with gemcitabine and erlotinib in patients with metastatic pancreatic cancer.

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    Daniel A Monti

    Full Text Available Preclinical data support further investigation of ascorbic acid in pancreatic cancer. There are currently insufficient safety data in human subjects, particularly when ascorbic acid is combined with chemotherapy.14 subjects with metastatic stage IV pancreatic cancer were recruited to receive an eight week cycle of intravenous ascorbic acid (three infusions per week, using a dose escalation design, along with standard treatment of gemcitabine and erlotinib. Of 14 recruited subjects enrolled, nine completed the study (three in each dosage tier. There were fifteen non-serious adverse events and eight serious adverse events, all likely related to progression of disease or treatment with gemcitabine or erlotinib. Applying RECIST 1.0 criteria, seven of the nine subjects had stable disease while the other two had progressive disease.These initial safety data do not reveal increased toxicity with the addition of ascorbic acid to gemcitabine and erlotinib in pancreatic cancer patients. This, combined with the observed response to treatment, suggests the need for a phase II study of longer duration.Clinicaltrials.gov NCT00954525.

  14. Phase I trial of erlotinib with radiation therapy in patients with glioblastoma multiforme: Results of North Central Cancer Treatment Group protocol N0177

    International Nuclear Information System (INIS)

    Krishnan, Sunil; Brown, Paul D.; Ballman, Karla V.; Fiveash, John B.; Uhm, Joon H.; Giannini, Caterina; Jaeckle, Kurt A.; Geoffroy, Francois J.; Nabors, L. Burt; Buckner, Jan C.

    2006-01-01

    Purpose: To evaluate the toxicity and maximum tolerated dose (MTD) of erlotinib plus radiation therapy (RT) in patients with glioblastoma multiforme (GBM) in a multicenter phase I trial. Methods and Materials: Patients were stratified on the basis of the use of enzyme-inducing anticonvulsants (EIACs). After resection or biopsy, patients were treated with erlotinib for 1 week before concurrent erlotinib and 6 weeks (60 Gy) of RT and maintained on erlotinib until progression. The erlotinib dose was escalated in cohorts of 3 starting at 100 mg/day. Results: Twenty patients were enrolled and 19 were evaluable for the MTD and efficacy endpoints. Of these patients, 14 were males and 5 were females, with a median age of 54 years. Seven had undergone biopsy only, 5 had subtotal resections, and 7 had gross total resections. The highest dose level was 150 mg/day erlotinib for patients not on EIACs (Group 1) and 200 mg/day for patients on EIACs (Group 2). MTD was not reached in either group. In Group 1 at 100 mg (n = 6) and at 150 mg (n = 4), only 1 dose-limiting toxicity (DLT) occurred (stomatitis at 100 mg). No DLTs have occurred in Group 2 at 100 mg (n = 3), 150 mg (n = 3), and 200 mg (n = 3). With a median follow-up of 52 weeks, progression was documented in 16 patients and 13 deaths occurred. Median time to progression was 26 weeks, and median survival was 55 weeks. Conclusion: Toxicity is acceptable at the current doses of erlotinib plus RT. The study was modified to include concurrent and adjuvant temozolomide, and accrual is in progress

  15. Randomized Phase II Trial of Erlotinib Alone or With Carboplatin and Paclitaxel in Patients Who Were Never or Light Former Smokers With Advanced Lung Adenocarcinoma: CALGB 30406 Trial

    Science.gov (United States)

    Jänne, Pasi A.; Wang, Xiaofei; Socinski, Mark A.; Crawford, Jeffrey; Stinchcombe, Thomas E.; Gu, Lin; Capelletti, Marzia; Edelman, Martin J.; Villalona-Calero, Miguel A.; Kratzke, Robert; Vokes, Everett E.; Miller, Vincent A.

    2012-01-01

    Purpose Erlotinib is clinically effective in patients with non–small-cell lung cancer (NSCLC) who have adenocarcinoma, are never or limited former smokers, or have EGFR mutant tumors. We investigated the efficacy of erlotinib alone or in combination with chemotherapy in patients with these characteristics. Patients and Methods Patients with advanced NSCLC (adenocarcinoma) who were epidermal growth factor receptor tyrosine kinase inhibitor and chemotherapy naive never or light former smokers (smokers of > 100 cigarettes and ≤ 10 pack years and quit ≥ 1 year ago) were randomly assigned to continuous erlotinib or in combination with carboplatin and paclitaxel (ECP) for six cycles followed by erlotinib alone. The primary end point was progression-free survival (PFS). Tissue collection was mandatory. Results PFS was similar (5.0 v 6.6 months; P = .1988) in patients randomly assigned to erlotinib alone (arm A; n = 81) or to ECP (arm B; n = 100). EGFR mutation analysis was possible in 91% (164 of 181) of patients, and EGFR mutations were detected in 40% (51 of 128) of never smokers and in 42% (15 of 36) of light former smokers. In arm A, response rate (70% v 9%), PFS (14.1 v 2.6 months), and overall survival (OS; 31.3 v 18.1 month) favored EGFR-mutant patients. In arm B, response rate (73% v 30%), PFS (17.2 v 4.8 months), and OS (38.1 v 14.4 months) favored EGFR-mutant patients. Incidence of grades 3 to 4 hematologic (2% v 49%; P < .001) and nonhematologic (24% v 52%; P < .001) toxicity was greater in patients treated with ECP. Conclusion Erlotinib and erlotinib plus chemotherapy have similar efficacy in clinically selected populations of patients with advanced NSCLC. EGFR mutations identify patients most likely to benefit. PMID:22547605

  16. Multi-parameter in vitro toxicity testing of crizotinib, sunitinib, erlotinib, and nilotinib in human cardiomyocytes

    International Nuclear Information System (INIS)

    Doherty, Kimberly R.; Wappel, Robert L.; Talbert, Dominique R.; Trusk, Patricia B.; Moran, Diarmuid M.; Kramer, James W.; Brown, Arthur M.; Shell, Scott A.; Bacus, Sarah

    2013-01-01

    Tyrosine kinase inhibitors (TKi) have greatly improved the treatment and prognosis of multiple cancer types. However, unexpected cardiotoxicity has arisen in a subset of patients treated with these agents that was not wholly predicted by pre-clinical testing, which centers around animal toxicity studies and inhibition of the human Ether-à-go-go-Related Gene (hERG) channel. Therefore, we sought to determine whether a multi-parameter test panel assessing the effect of drug treatment on cellular, molecular, and electrophysiological endpoints could accurately predict cardiotoxicity. We examined how 4 FDA-approved TKi agents impacted cell viability, apoptosis, reactive oxygen species (ROS) generation, metabolic status, impedance, and ion channel function in human cardiomyocytes. The 3 drugs clinically associated with severe cardiac adverse events (crizotinib, sunitinib, nilotinib) all proved to be cardiotoxic in our in vitro tests while the relatively cardiac-safe drug erlotinib showed only minor changes in cardiac cell health. Crizotinib, an ALK/MET inhibitor, led to increased ROS production, caspase activation, cholesterol accumulation, disruption in cardiac cell beat rate, and blockage of ion channels. The multi-targeted TKi sunitinib showed decreased cardiomyocyte viability, AMPK inhibition, increased lipid accumulation, disrupted beat pattern, and hERG block. Nilotinib, a second generation Bcr-Abl inhibitor, led to increased ROS generation, caspase activation, hERG block, and an arrhythmic beat pattern. Thus, each drug showed a unique toxicity profile that may reflect the multiple mechanisms leading to cardiotoxicity. This study demonstrates that a multi-parameter approach can provide a robust characterization of drug-induced cardiomyocyte damage that can be leveraged to improve drug safety during early phase development. - Highlights: • TKi with known adverse effects show unique cardiotoxicity profiles in this panel. • Crizotinib increases ROS, apoptosis, and

  17. Dvorak. Concerto pour violoncelle / Francis Dresel

    Index Scriptorium Estoniae

    Dresel, Francis

    1992-01-01

    Uuest heliplaadist "Dvorak. Concerto pour violoncelle; Schumann: Concerto pour violoncelle. Orchestre Symphonique d'Estonie, Orchestre Symphonique de la Radio TV d'URSS, Neeme Järvi" Vogue "Archives Sovietiques" 651033 1978

  18. Erlotinib usage after prior treatment with gefitinib in advanced non-small cell lung cancer: A clinical perspective and review of published literature.

    Science.gov (United States)

    Singh, Navneet; Jindal, Aditya; Behera, Digambar

    2014-12-10

    Erlotinib and gefitinib are among the most widely researched, used and available molecularly targeted therapies for treatment of advanced non-small cell lung cancer (NSCLC). They are both tyrosine kinase inhibitors (TKIs) of the epidermal growth factor receptor (EGFR). In the past decade, there have been reports on clinical benefit from use of erlotinib after gefitinib failure in NSCLC patients. A review of published literature on this focussed topic is provided herein. Pooled analysis of published literature shows that majority of patients were female (60.6%), non-smokers (64.5%), had adenocarcinoma histology (88.3%) and were of East Asian ethnicity (92.3%). Presence of sensitizing EGFR mutation was detected in 48.4% of subjects. Disease control rates with prior gefitinib therapy and with subsequent erlotinib treatment were 79.4% and 45.4% respectively. Based upon our review, the most important predictive factor for clinical benefit from erlotinib identified was previous response to gefitinib. The exact explanations for the potential benefit from erlotinib use in this patient population is still not known and further studies are required to determine the role of molecular mechanisms especially those related to resistance to initial EGFR TKI therapy.

  19. OPTIMAL and ENSURE trials-based combined cost-effectiveness analysis of erlotinib versus chemotherapy for the first-line treatment of Asian patients with non-squamous non-small-cell lung cancer

    Science.gov (United States)

    Zhang, Pengfei; Hutton, David; Li, Qiu

    2018-01-01

    Objectives Erlotinib, the first generation of epidermoid growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI), has been recommended as an essential treatment in patients with non-small-cell lung cancer (NSCLC) with EGFR mutation. Although it has improved progression-free survival (PFS), overall survival (OS) was limited and erlotinib can be expensive. This cost-effectiveness analysis compares erlotinib monotherapy with gemcitabine-included doublet chemotherapy. Setting First-line treatment of Asian patients with NSCLC with EGFR mutation. Methods A Markov model was created based on the results of the ENSURE (NCT01342965) and OPTIMAL (CTONG-0802) trials which evaluated erlotinib and chemotherapy. The model simulates cancer progression and all causes of death. All medical costs were calculated from the perspective of the Chinese healthcare system. Main outcome measures The primary outcomes are costs, quality-adjusted life years (QALYs) and incremental cost-effectiveness ratios (ICERs). Results The combined PFS was 11.81 months and 5.1 months for erlotinib and chemotherapy, respectively, while the OS was reversed at 24.68 months for erlotinib and 26.16 months for chemotherapy. The chemotherapy arm gained 0.13 QALYs compared with erlotinib monotherapy (1.17 QALYs vs 1.04 QALYs), while erlotinib had lower costs ($55 230 vs $77 669), resulting in an ICER of $174 808 per QALY for the chemotherapy arm, which exceeds three times the Chinese GDP per capita. The most influential factors were the health utility of PFS, the cost of erlotinib and the health utility of progressed disease. Conclusion Erlotinib monotherapy may be acceptable as a cost-effective first-line treatment for NSCLC compared with gemcitabine-based chemotherapy. The results were robust to changes in assumptions. Trial registration number NCT01342965 and CTONG-0802. PMID:29654023

  20. When It Rains, It Pours

    Science.gov (United States)

    Mills, Linda

    2012-01-01

    "It's raining, it's pouring, the old man is snoring!" "The itsy, bitsy spider crawled up the waterspout, down came the rain and washed the spider out. Out came the sun and dried up all the rain, and the itsy, bitsy spider went up the spout again." What do children's nursery rhymes have to do with the school library? The author begins by telling a…

  1. Prediction of sensitivity to gefitinib/erlotinib for EGFR mutations in NSCLC based on structural interaction fingerprints and multilinear principal component analysis.

    Science.gov (United States)

    Zou, Bin; Lee, Victor H F; Yan, Hong

    2018-03-07

    Non-small cell lung cancer (NSCLC) with activating EGFR mutations, especially exon 19 deletions and the L858R point mutation, is particularly responsive to gefitinib and erlotinib. However, the sensitivity varies for less common and rare EGFR mutations. There are various explanations for the low sensitivity of EGFR exon 20 insertions and the exon 20 T790 M point mutation to gefitinib/erlotinib. However, few studies discuss, from a structural perspective, why less common mutations, like G719X and L861Q, have moderate sensitivity to gefitinib/erlotinib. To decode the drug sensitivity/selectivity of EGFR mutants, it is important to analyze the interaction between EGFR mutants and EGFR inhibitors. In this paper, the 30 most common EGFR mutants were selected and the technique of protein-ligand interaction fingerprint (IFP) was applied to analyze and compare the binding modes of EGFR mutant-gefitinib/erlotinib complexes. Molecular dynamics simulations were employed to obtain the dynamic trajectory and a matrix of IFPs for each EGFR mutant-inhibitor complex. Multilinear Principal Component Analysis (MPCA) was applied for dimensionality reduction and feature selection. The selected features were further analyzed for use as a drug sensitivity predictor. The results showed that the accuracy of prediction of drug sensitivity was very high for both gefitinib and erlotinib. Targeted Projection Pursuit (TPP) was used to show that the data points can be easily separated based on their sensitivities to gefetinib/erlotinib. We can conclude that the IFP features of EGFR mutant-TKI complexes and the MPCA-based tensor object feature extraction are useful to predict the drug sensitivity of EGFR mutants. The findings provide new insights for studying and predicting drug resistance/sensitivity of EGFR mutations in NSCLC and can be beneficial to the design of future targeted therapies and innovative drug discovery.

  2. Gefitinib provides similar effectiveness and improved safety than erlotinib for advanced non-small cell lung cancer: A meta-analysis.

    Science.gov (United States)

    Zhang, Wenxiong; Wei, Yiping; Yu, Dongliang; Xu, Jianjun; Peng, Jinhua

    2018-04-01

    The epidermal growth factor receptor tyrosine kinase inhibitors gefitinib and erlotinib are effective for advanced non-small cell lung cancer (NSCLC). This meta-analysis compared their effectiveness and safety. We searched systematically in PubMed, ScienceDirect, The Cochrane Library, Scopus, Ovid MEDLINE, EMBASE, Web of Science, and Google Scholar for relevant clinical trials regarding gefitinib versus erlotinib for NSCLC. Antitumor effectiveness (overall survival [OS], progression-free survival [PFS], objective response rate [ORR] and disease control rate [DCR]) and adverse effects [AEs]) were assessed. Forty studies comprising 9376 participants were included. The results suggested that gefitinib and erlotinib are effective for advanced NSCLC with comparable PFS (95% confidence intervals [CI]: 0.98-1.11, P = .15), OS (95% CI: 0.93-1.19, P = .45), ORR (95% CI: 0.99-1.16, P = .07), and DCR (95% CI: 0.92-1.03, P = .35). For erlotinib, dose reduction was significantly more frequent (95% CI: 0.10-0.57, P = .001) as were grade 3 to 5 AEs (95% CI: 0.36-0.79, P = .002). In the subgroup analysis, the erlotinib group had a significant higher rate and severity of skin rash, nausea/vomiting, fatigue, and stomatitis. Gefitinib was proven to be the better choice for advanced NSCLC, with equal antitumor effectiveness and fewer AEs compared with erlotinib. Further large-scale, well-designed randomized controlled trials are warranted to confirm our validation.

  3. Molecular Subgroup Analysis of Clinical Outcomes in a Phase 3 Study of Gemcitabine and Oxaliplatin with or without Erlotinib in Advanced Biliary Tract Cancer

    Directory of Open Access Journals (Sweden)

    Seung Tae Kim

    2015-02-01

    Full Text Available BACKGROUND: We previously reported that the addition of erlotinib to gemcitabine and oxaliplatin (GEMOX resulted in greater antitumor activity and might be a treatment option for patients with biliary tract cancers (BTCs. Molecular subgroup analysis of treatment outcomes in patients who had specimens available for analysis was undertaken. METHODS: Epidermal growth factor receptor (EGFR, KRAS, and PIK3CA mutations were evaluated using peptide nucleic acid–locked nucleic acid polymerase chain reaction clamp reactions. Survival and response rates (RRs were analyzed according to the mutational status. Sixty-four patients (48.1% were available for mutational analysis in the chemotherapy alone group and 61 (45.1% in the chemotherapy plus erlotinib group. RESULTS: 1.6% (2/116 harbored an EGFR mutation (2 patients; exon 20, 9.6% (12/121 harbored a KRAS mutation (12 patients; exon 2, and 9.6% (12/118 harbored a PIK3CA mutation (10 patients, exon 9 and 2 patients, exon 20. The addition of erlotinib to GEMOX in patients with KRAS wild-type disease (n = 109 resulted in significant improvements in overall response compared with GEMOX alone (30.2% vs 12.5%, P = .024. In 95 patients with both wild-type KRAS and PIK3CA, there was evidence of a benefit associated with the addition of erlotinib to GEMOX with respect to RR as compared with GEMOX alone (P = .04. CONCLUSION: This study demonstrates that KRAS mutational status might be considered a predictive biomarker for the response to erlotinib in BTCs. Additionally, the mutation status of PIK3CA may be a determinant for adding erlotinib to chemotherapy in KRAS wild-type BTCs.

  4. Characterization and response of newly developed high-grade glioma cultures to the tyrosine kinase inhibitors, erlotinib, gefitinib and imatinib

    International Nuclear Information System (INIS)

    Kinsella, Paula; Howley, Rachel; Doolan, Padraig; Clarke, Colin; Madden, Stephen F.; Clynes, Martin; Farrell, Michael; Amberger-Murphy, Verena

    2012-01-01

    High-grade gliomas (HGG), are the most common aggressive brain tumours in adults. Inhibitors targeting growth factor signalling pathways in glioma have shown a low clinical response rate. To accurately evaluate response to targeted therapies further in vitro studies are necessary. Growth factor pathway expression using epidermal growth factor receptor (EGFR), mutant EGFR (EGFRvIII), platelet derived growth factor receptor (PDGFR), C-Kit and C-Abl together with phosphatase and tensin homolog (PTEN) expression and downstream activation of AKT and phosphorylated ribosomal protein S6 (P70S6K) was analysed in 26 primary glioma cultures treated with the tyrosine kinase inhibitors (TKIs) erlotinib, gefitinib and imatinib. Response to TKIs was assessed using 50% inhibitory concentrations (IC 50 ). Response for each culture was compared with the EGFR/PDGFR immunocytochemical pathway profile using hierarchical cluster analysis (HCA) and principal component analysis (PCA). Erlotinib response was not strongly associated with high expression of the growth factor pathway components. PTEN expression did not correlate with response to any of the three TKIs. Increased EGFR expression was associated with gefitinib response; increased PDGFR-α expression was associated with imatinib response. The results of this in vitro study suggest gefitinib and imatinib may have therapeutic potential in HGG tumours with a corresponding growth factor receptor expression profile. -- Highlights: ► Non-responders had low EGFR expression, high PDGFR-β, and a low proliferation rate. ► PTEN is not indicative of response to a TKI. ► Erlotinib response was not associated with expression of the proteins examined. ► Imatinib-response correlated with expression of PDGFR-α. ► Gefitinib response correlated with increased expression of EGFR.

  5. Des semences pour vivre | CRDI - Centre de recherches pour le ...

    International Development Research Centre (IDRC) Digital Library (Canada)

    12 juil. 2011 ... Partout au Canada, le marché des aliments biologiques ne cesse de croître, ... du Centre de recherches pour le développement international (CRDI) et d'Inter ... des variétés de semences et des modes de culture traditionnels, face à ... La protection de l'accès à l'eau contre les effets de l'étalement urbain et ...

  6. Comparison of effectiveness and adverse effects of gefitinib, erlotinib and icotinib among patients with non-small cell lung cancer: A network meta-analysis.

    Science.gov (United States)

    Liu, Yuanyuan; Zhang, Yu; Feng, Gangling; Niu, Qiang; Xu, Shangzhi; Yan, Yizhong; Li, Shugang; Jing, Mingxia

    2017-11-01

    The present network meta-analysis aimed to compare the effectiveness and adverse effects of gefitinib, erlotinib and icotinib in the treatment of patients with non-small cell lung cancer (NSCLC). Two reviewers searched the Cochrane, PubMed, Embase, ScienceDirect, China National Knowledge Infrastructure, VIP Database for Chinese Technical Periodicals and Wanfang databases for relevant studies. Studies were then screened and evaluated, and data was extracted. End-points evaluated for NSCLC included complete response (CR), partial response (PR), stable disease (SD), progressive disease (PD), overall response rate (ORR), disease control rate (DCR), progression-free survival (PFS), median survival time (MST) and adverse effects, including rash, diarrhea, nausea and vomiting, fatigue and abnormal liver function. For the analysis of incorporated studies, RevMan, SPSS, R and Stata software were used. A total of 43 studies with 7,168 patients were included in the network meta-analysis. No significant differences were observed in CR, PR, SD, PD, ORR or DCR between gefitinib, erlotinib and icotinib by using network meta analysis. Compared with gefitinib, erlotinib resulted in a higher rate of nausea and vomiting [adjusted odds ratio (OR)=2.0; 95% credible interval, 1.1-3.7]. However, no significant differences were observed in the rates of rash, diarrhea, fatigue or abnormal liver function using network meta-analysis. Compared with erlotinib, gefitinib resulted in a lower SD rate [OR=0.86; 95% confidence interval (CI): 0.75-0.99; P=0.04], and lower rates of rash (OR=0.45; 95% CI, 0.36-0.55; Panalysis of two congruent drugs. However, gefitinib resulted in a higher rate of rash compared with icotinib (OR=1.57; 95% CI, 1.18-2.09; P=0.002). Otherwise, no significant differences were observed in CR, PR, PD, ORR, DCR and abnormal liver function between gefitinib, erlotinib and icotinib through meta-analysis of two congruent drugs. The PFS rate for gefitinib, erlotinib and icotinib

  7. Exogenous Restoration of TUSC2 Expression Induces Responsiveness to Erlotinib in Wildtype Epidermal Growth Factor Receptor (EGFR Lung Cancer Cells through Context Specific Pathways Resulting in Enhanced Therapeutic Efficacy.

    Directory of Open Access Journals (Sweden)

    Bingbing Dai

    Full Text Available Expression of the tumor suppressor gene TUSC2 is reduced or absent in most lung cancers and is associated with worse overall survival. In this study, we restored TUSC2 gene expression in several wild type EGFR non-small cell lung cancer (NSCLC cell lines resistant to the epidermal growth factor receptor (EGFR tyrosine kinase inhibitor erlotinib and analyzed their sensitivity to erlotinib in vitro and in vivo. A significant inhibition of cell growth and colony formation was observed with TUSC2 transient and stable expression. TUSC2-erlotinib cooperativity in vitro could be reproduced in vivo in subcutaneous tumor growth and lung metastasis formation lung cancer xenograft mouse models. Combination treatment with intravenous TUSC2 nanovesicles and erlotinib synergistically inhibited tumor growth and metastasis, and increased apoptotic activity. High-throughput qRT-PCR array analysis enabling multi-parallel expression profile analysis of eighty six receptor and non-receptor tyrosine kinase genes revealed a significant decrease of FGFR2 expression level, suggesting a potential role of FGFR2 in TUSC2-enhanced sensitivity to erlotinib. Western blots showed inhibition of FGFR2 by TUSC2 transient transfection, and marked increase of PARP, an apoptotic marker, cleavage level after TUSC2-erlotinb combined treatment. Suppression of FGFR2 by AZD4547 or gene knockdown enhanced sensitivity to erlotinib in some but not all tested cell lines. TUSC2 inhibits mTOR activation and the latter cell lines were responsive to the mTOR inhibitor rapamycin combined with erlotinib. These results suggest that TUSC2 restoration in wild type EGFR NSCLC may overcome erlotinib resistance, and identify FGFR2 and mTOR as critical regulators of this activity in varying cellular contexts. The therapeutic activity of TUSC2 could extend the use of erlotinib to lung cancer patients with wildtype EGFR.

  8. Characterization and response of newly developed high-grade glioma cultures to the tyrosine kinase inhibitors, erlotinib, gefitinib and imatinib.

    LENUS (Irish Health Repository)

    Kinsella, Paula

    2012-03-10

    High-grade gliomas (HGG), are the most common aggressive brain tumours in adults. Inhibitors targeting growth factor signalling pathways in glioma have shown a low clinical response rate. To accurately evaluate response to targeted therapies further in vitro studies are necessary. Growth factor pathway expression using epidermal growth factor receptor (EGFR), mutant EGFR (EGFRvIII), platelet derived growth factor receptor (PDGFR), C-Kit and C-Abl together with phosphatase and tensin homolog (PTEN) expression and downstream activation of AKT and phosphorylated ribosomal protein S6 (P70S6K) was analysed in 26 primary glioma cultures treated with the tyrosine kinase inhibitors (TKIs) erlotinib, gefitinib and imatinib. Response to TKIs was assessed using 50% inhibitory concentrations (IC(50)). Response for each culture was compared with the EGFR\\/PDGFR immunocytochemical pathway profile using hierarchical cluster analysis (HCA) and principal component analysis (PCA). Erlotinib response was not strongly associated with high expression of the growth factor pathway components. PTEN expression did not correlate with response to any of the three TKIs. Increased EGFR expression was associated with gefitinib response; increased PDGFR-α expression was associated with imatinib response. The results of this in vitro study suggest gefitinib and imatinib may have therapeutic potential in HGG tumours with a corresponding growth factor receptor expression profile.

  9. Network meta-analysis of erlotinib, gefitinib, afatinib and icotinib in patients with advanced non-small-cell lung cancer harboring EGFR mutations.

    Science.gov (United States)

    Liang, Wenhua; Wu, Xuan; Fang, Wenfeng; Zhao, Yuanyuan; Yang, Yunpeng; Hu, Zhihuang; Xue, Cong; Zhang, Jing; Zhang, Jianwei; Ma, Yuxiang; Zhou, Ting; Yan, Yue; Hou, Xue; Qin, Tao; Dinglin, Xiaoxiao; Tian, Ying; Huang, Peiyu; Huang, Yan; Zhao, Hongyun; Zhang, Li

    2014-01-01

    Several EGFR-tyrosine kinase inhibitors (EGFR-TKIs) including erlotinib, gefitinib, afatinib and icotinib are currently available as treatment for patients with advanced non-small-cell lung cancer (NSCLC) who harbor EGFR mutations. However, no head to head trials between these TKIs in mutated populations have been reported, which provides room for indirect and integrated comparisons. We searched electronic databases for eligible literatures. Pooled data on objective response rate (ORR), progression free survival (PFS), overall survival (OS) were calculated. Appropriate networks for different outcomes were established to incorporate all evidences. Multiple-treatments comparisons (MTCs) based on Bayesian network integrated the efficacy and specific toxicities of all included treatments. Twelve phase III RCTs that investigated EGFR-TKIs involving 1821 participants with EGFR mutation were included. For mutant patients, the weighted pooled ORR and 1-year PFS of EGFR-TKIs were significant superior to that of standard chemotherapy (ORR: 66.6% vs. 30.9%, OR 5.46, 95%CI 3.59 to 8.30, Picotinib (19%, 29%, NA, NA), respectively. However, afatinib and erlotinib showed significant severer rash and diarrhea compared with gefitinib and icotinib. The current study indicated that erlotinib, gefitinib, afatinib and icotinib shared equivalent efficacy but presented different efficacy-toxicity pattern for EGFR-mutated patients. Erlotinib and afatinib revealed potentially better efficacy but significant higher toxicities compared with gefitinib and icotinib.

  10. A receptor tyrosine kinase ROR1 inhibitor (KAN0439834 induced significant apoptosis of pancreatic cells which was enhanced by erlotinib and ibrutinib.

    Directory of Open Access Journals (Sweden)

    Amir Hossein Daneshmanesh

    Full Text Available There is a great unmet medical need in pancreatic carcinoma (PC for novel drugs with other mechanisms of action than existing. PC cells express the onco-fetal RTK ROR1, absent on most normal post-partem cells. ROR1 is involved in proliferation, survival, EMT and metastasis of tumor cells in various malignancies. A small molecule inhibitor (KAN0439834 (530 Da targeting the TK domain of ROR1 was developed and the activity in ROR1 expressing human PC cell lines (n = 8 evaluated. The effects were compared to a murine mAb against the external part of ROR1, gemcitabine, erlotinib and ibrutinib. KAN0439834 induced significant apoptosis of the tumor cells. EC50 values for KAN0439834 varied between 250-650 nM depending on the cell line. The corresponding values for erlotinib and ibrutinib were 10-40 folds higher. KAN0439834 was much more effective in inducing tumor cell death than the ROR1 mAb although both inhibited ROR1 phosphorylation and downstream non-canonical Wnt pathway molecules. Combination of KAN0439834 with erlotinib or ibrutinib had significant additive effects on tumor cell death. A first-in-class small molecule ROR1 inhibitor (KAN0439834 showed promising in vitro activity against a number of human PC cell lines. Interesting is the additive effects of erlotinib and ibrutinib which warrants further studies as both these agents are in clinical trials for pancreatic carcinoma.

  11. Cross-market cost-effectiveness analysis of erlotinib as first-line maintenance treatment for patients with stable non-small cell lung cancer

    Directory of Open Access Journals (Sweden)

    Vergnenègre A

    2012-01-01

    Full Text Available Alain Vergnenègre1, Joshua A Ray2, Christos Chouaid3, Francesco Grossi4, Helge G Bischoff5, David F Heigener6, Stefan Walzer21Department of Pneumology, Hôpital du Cluzeau, Limoges, France; 2Global Health Economics and Strategic Pricing, F Hoffmann-La Roche Ltd, Basel, Switzerland; 3Respiratory Service, Hôpital Saint Antoine, Paris, France; 4Lung Cancer Unit, National Institute for Cancer Research, Genoa, Italy; 5Thoracic Oncology, Onkologie Thoraxklinik Heidelberg, Heidelberg, Germany; 6Department of Thoracic Oncology, Krankenhaus Großhansdorf, Großhansdorf, GermanyBackground: Platinum-doublet, first-line treatment of locally advanced or metastatic non-small cell lung cancer (NSCLC is limited to 4–6 cycles. An alternative strategy used to prolong the duration of first-line treatment and extend survival in metastatic NSCLC is first-line maintenance therapy. Erlotinib was approved for first-line maintenance in a stable disease population following results from a randomized, controlled Phase III trial comparing erlotinib with best supportive care. We aimed to estimate the incremental cost-effectiveness of erlotinib 150 mg/day versus best supportive care when used as first-line maintenance therapy for patients with locally advanced or metastatic NSCLC and stable disease.Methods: An economic decision model was developed using patient-level data for progression-free survival and overall survival from the SATURN (SequentiAl Tarceva in UnResectable NSCLC study. An area under the curve model was developed; all patients entered the model in the progression-free survival health state and, after each month, moved to progression or death. A time horizon of 5 years was used. The model was conducted from the perspective of national health care payers in France, Germany, and Italy. Probabilistic sensitivity analyses were performed.Results: Treatment with erlotinib in first-line maintenance resulted in a mean life expectancy of 1.39 years in all countries

  12. Randomised phase III trial of concurrent chemoradiotherapy with extended nodal irradiation and erlotinib in patients with inoperable oesophageal squamous cell cancer.

    Science.gov (United States)

    Wu, Shi-Xiu; Wang, Lv-Hua; Luo, Hong-Lei; Xie, Cong-Ying; Zhang, Xue-Bang; Hu, Wei; Zheng, An-Ping; Li, Duo-Jie; Zhang, Hong-Yan; Xie, Cong-Hua; Lian, Xi-Long; Du, De-Xi; Chen, Ming; Bian, Xiu-Hua; Tan, Bang-Xian; Jiang, Hao; Zhang, Hong-Bo; Wang, Jian-Hua; Jing, Zhao; Xia, Bing; Zhang, Ni; Zhang, Ping; Li, Wen-Feng; Zhao, Fu-Jun; Tian, Zhi-Feng; Liu, Hui; Huang, Ke-Wei; Hu, Jin; Xie, Rui-Fei; Du, Lin; Li, Gang

    2018-04-01

    This randomised phase III study was conducted to investigate the efficacy of extended nodal irradiation (ENI) and/or erlotinib in inoperable oesophageal squamous cell cancer (ESCC). Patients with histologically confirmed locally advanced ESCC or medically inoperable disease were randomly assigned (ratio 1:1:1:1) to one of four treatment groups: group A, radiotherapy adoption of ENI with two cycles of concurrent TP chemotherapy (paclitaxel 135 mg/m 2  day 1 and cisplatin 20 mg/m 2 days 1-3, every 4 weeks) plus erlotinib (150 mg per day during chemoradiotherapy); group B, radiotherapy adoption of ENI with two cycles of concurrent TP; group C, radiotherapy adoption of conventional field irradiation (CFI) with two cycles of concurrent TP plus erlotinib; group D, radiotherapy adoption of CFI with two cycles of concurrent TP. A total of 352 patients (88 assigned to each treatment group) were enrolled. The 2-year overall survival rates of group A, B, C and D were 57.8%, 49.9%, 44.9% and 38.7%, respectively (P = 0.015). Group A significantly improved 2-year overall survival compared with group D. The ENI significantly improved overall survival in patients with inoperable ESCC (P = 0.014). The addition of erlotinib significantly decreased loco-regional recurrence (P = 0.042). Aside from rash and radiation oesophagitis, the incidence of grade 3 or greater toxicities did not differ among 4 groups. Chemoradiotherapy with ENI and erlotinib might represent a substantial improvement on the standard of care for inoperable ESCC. ENI alone should be adopted in concurrent chemoradiotherapy for ESCC patients. Copyright © 2018 Elsevier Ltd. All rights reserved.

  13. Combination chemotherapy with intermittent erlotinib and pemetrexed for pretreated patients with advanced non-small cell lung cancer: a phase I dose-finding study

    International Nuclear Information System (INIS)

    Minami, Seigo; Tachibana, Isao; Komuta, Kiyoshi; Kawase, Ichiro; Kijima, Takashi; Takahashi, Ryo; Kida, Hiroshi; Nakatani, Takeshi; Hamaguchi, Masanari; Takeuchi, Yoshiko; Nagatomo, Izumi; Yamamoto, Suguru

    2012-01-01

    Erlotinib and pemetrexed have been approved for the second-line treatment of non-small cell lung cancer (NSCLC). These two agents have different mechanisms of action. Combined treatment with erlotinib and pemetrexed could potentially augment the antitumor activity of either agent alone. In the present study, we investigated the safety profile of combined administration of the two agents in pretreated NSCLC patients. A phase I dose-finding study (Trial registration: UMIN000002900) was performed in patients with stage III/IV nonsquamous NSCLC whose disease had progressed on or after receiving first-line chemotherapy. Patients received 500 mg/m 2 of pemetrexed intravenously every 21 days and erlotinib (100 mg at Level 1 and 150 mg at Level 2) orally on days 2–16. Twelve patients, nine males and three females, were recruited. Patient characteristics included a median age of 66 years (range, 48–78 years), stage IV disease (nine cases), adenocarcinoma (seven cases) and activating mutation-positives in the epidermal growth factor receptor gene (two cases). Treatment was well-tolerated, and the recommended dose of erlotinib was fixed at 150 mg. Dose-limiting toxicities were experienced in three patients and included: grade 3 elevation of serum alanine aminotransferase, repetitive grade 4 neutropenia that required reduction of the second dose of pemetrexed and grade 3 diarrhea. No patient experienced drug-induced interstitial lung disease. Three patients achieved a partial response and stable disease was maintained in five patients. Combination chemotherapy of intermittent erlotinib with pemetrexed was well-tolerated, with promising efficacy against pretreated advanced nonsquamous NSCLC

  14. Report of a Multicenter Phase II Trial Testing a Combination of Biweekly Bevacizumab and Daily Erlotinib in Patients With Unresectable Biliary Cancer: A Phase II Consortium Study

    Science.gov (United States)

    Lubner, Sam J.; Mahoney, Michelle R.; Kolesar, Jill L.; LoConte, Noelle K.; Kim, George P.; Pitot, Henry C.; Philip, Philip A.; Picus, Joel; Yong, Wei-Peng; Horvath, Lisa; Van Hazel, Guy; Erlichman, Charles E.; Holen, Kyle D.

    2010-01-01

    Purpose Biliary cancers overexpress epidermal growth factor receptor (EGFR), and angiogenesis has been correlated with poor outcome. Erlotinib, an EGFR tyrosine kinase inhibitor, and bevacizumab, a vascular endothelial growth factor (VEGF) inhibitor have each been shown to have activity in biliary cancer. The primary objective of this study was to evaluate the response rate by Response Evaluation Criteria in Solid Tumors (RECIST). Secondary end points included overall survival (OS), time to progression (TTP), VEGF levels, and molecular studies of EGFR and k-ras. Patients and Methods Eligible patients had advanced cholangiocarcinoma or gallbladder cancer. Patients were treated with bevacizumab 5 mg/kg intravenously on days 1 and 15 and erlotinib 150 mg by mouth daily on days 1 through 28. Responses were evaluated by RECIST. VEGF levels were collected, and samples were analyzed for EGFR mutation by polymerase chain reaction. Results Fifty-three eligible patients were enrolled at eight sites. Of 49 evaluable patients, six (12%; 95% CI, 6% to 27%) had a confirmed partial response. Stable disease was documented in another 25 patients (51%). Rash was the most common grade 3 toxicity. Four patients had grade 4 toxicities. Median OS was 9.9 months, and TTP was 4.4 months. Low repeats (G k-ras Q38 genotype (wild type) were associated with improved outcomes. Conclusion Combination chemotherapy with bevacizumab and erlotinib showed clinical activity with infrequent grade 3 and 4 adverse effects in patients with advanced biliary cancers. On the basis of preliminary molecular analysis, presence of a k-ras mutation may alter erlotinib efficacy. The combination of bevacizumab and erlotinib may be a therapeutic alternative in patients with advanced biliary cancer. PMID:20530271

  15. Metabolic tumor burden as marker of outcome in advanced EGFR wild-type NSCLC patients treated with erlotinib

    DEFF Research Database (Denmark)

    Winther-Larsen, Anne; Fledelius, Joan; Sorensen, Boe Sandahl

    2016-01-01

    OBJECTIVES: Accurate estimation of the prognosis of advanced non-small cell lung cancer (NSCLC) patients is essential before initiation of palliative treatment; especially in the second and third-line setting. This study was conducted in order to evaluate tumor burden measured on an 2'-deoxy-2...... a prospectively collected cohort. An F-18-FDG-PET/CT scan was conducted prior to erlotinib treatment and tumor burden was measured in terms of metabolic tumor volume (MTV) and total lesion glycolysis (TLG). Median values of MTV and TLG were used for dichotomization of patients. Survival outcome was compared...... between groups.RESULTS: MTV and TLG could be measured in 49 patients. High values of MTV and TLG were significantly correlated with shorter PFS (p

  16. Heterogeneous resistance mechanisms in an EGFR exon 19-mutated non-small cell lung cancer patient treated with erlotinib

    DEFF Research Database (Denmark)

    Santoni-Rugiu, Eric; Grauslund, Morten; Melchior, Linea C.

    2017-01-01

    Patients with epidermal growth factor receptor (EGFR) gene-mutated non-small cell lung cancer (NSCLC) obtain substantial clinical benefit from EGFR tyrosine-kinase inhibitors (TKIs), but will ultimately develop TKI-resistance resulting in median progression-free survival of 9–15 months during first......-line TKI-therapy. However, type and timing of TKI-resistance cannot be predicted and several mechanisms may simultaneously/subsequently occur during TKI-treatment. In this respect, we present a 49 year-old Caucasian male ex-smoker with metastatic pulmonary adenocarcinoma (ADC) that concomitantly harbored...... for SCLC combined with erlotinib continuation was implemented obtaining significant objective response. However, after completing 6 cycles of this combination, new pulmonary and hepatic metastases appeared and showed persistence of the original EGFR- and FGFR3-mutated ADC phenotype together...

  17. Erlotinib no controlo tumoral prolongado do carcinoma do pulmão de não pequenas células avançado (CPNPC

    Directory of Open Access Journals (Sweden)

    Teresa Guimarães

    2008-10-01

    Full Text Available Resumo: Os autores apresentam um caso clínico de um doente de raça caucasiana, sexo masculino, de 59 anos, não fumador, com um carcinoma do pulmão de não pequenas células (CPNPC, avançado, com 3 anos de follow-up, que se encontra actualmente a realizar tratamento com erlotinib, desde há 18 meses, após falência de mais de uma linha de quimioterapia, sem evidência de progressão oncológica. O doente evidencia excelente qualidade de vida, sintomatologia controlada, recuperação da capacidade de tolerância ao esforço e mantém a sua actividade profissional. O tratamento com erlotinib tem sido globalmente bem tolerado, embora exibindo toxicidade cutânea grau 1.Rev Port Pneumol 2008; XIV (Supl 3: S9-S15 Abstract: The authors present a clinical case of a caucasian male patient, 59 years-old, non-smoker, with an advanced non-small cell lung carcinoma (NSCLC, with 3 years of follow-up, received erlotinib for 18 months, after failure of more than one chemotherapy schedule, without evidence of oncologic progression. The patient evidences excellent quality of life, controlled sintomatology, recovery of the capacity of tolerance to the effort and it maintains his professional activities. The treatment with erlotinib has been well tolerated, although exhibiting grade 1 cutaneous toxicity.Rev Port Pneumol 2008; XIV (Supl 3: S9-S15 Palavras-chave: Carcinoma do pulmão de não pequenas células avançado ou metastático, CPNPC, erlotinib, inibi-dores da tirosina quinase (HER1/EGFR, quimioterapia, Key-words: Locally advanced or metastatic non-small cell lung cancer, NSCLC, erlotinib, thyrosine kinase epidermal growth factor receptor inhibitor (HER1/ EGFR, chemotherapy

  18. Phase I Study of Conformal Radiotherapy and Concurrent Full-Dose Gemcitabine With Erlotinib for Unresected Pancreatic Cancer

    International Nuclear Information System (INIS)

    Robertson, John M.; Margolis, Jeffrey; Jury, Robert P.; Balaraman, Savitha; Cotant, Matthew B.; Ballouz, Samer; Boxwala, Iqbal G.; Jaiyesimi, Ishmael A.; Nadeau, Laura; Hardy-Carlson, Maria; Marvin, Kimberly S.; Wallace, Michelle; Ye Hong

    2012-01-01

    Purpose: To determine the recommended dose of radiotherapy when combined with full-dose gemcitabine and erlotinib for unresected pancreas cancer. Methods and Materials: Patients with unresected pancreatic cancer (Zubrod performance status 0–2) were eligible for the present study. Gemcitabine was given weekly for 7 weeks (1,000 mg/m 2 ) with erlotinib daily for 8 weeks (100 mg). A final toxicity assessment was performed in Week 9. Radiotherapy (starting at 30 Gy in 2-Gy fractions, 5 d/wk) was given to the gross tumor plus a 1-cm margin starting with the first dose of gemcitabine. A standard 3 plus 3 dose escalation (an additional 4 Gy within 2 days for each dose level) was used, except for the starting dose level, which was scheduled to contain 6 patients. In general, Grade 3 or greater gastrointestinal toxicity was considered a dose-limiting toxicity, except for Grade 3 anorexia or Grade 3 fatigue alone. Results: A total of 20 patients were treated (10 men and 10 women). Nausea, vomiting, and infection were significantly associated with the radiation dose (p = .01, p = .03, and p = .03, respectively). Of the 20 patients, 5 did not complete treatment and were not evaluable for dose-escalation purposes (3 who developed progressive disease during treatment and 2 who electively discontinued it). Dose-limiting toxicity occurred in none of 6 patients at 30 Gy, 2 of 6 at 34 Gy, and 1 of 3 patients at 38 Gy. Conclusion: The results of the present study have indicated that the recommended Phase II dose is 30 Gy in 15 fractions.

  19. Factors Associated with Adherence to and Treatment Duration of Erlotinib Among Patients with Non-Small Cell Lung Cancer.

    Science.gov (United States)

    Hess, Lisa M; Louder, Anthony; Winfree, Katherine; Zhu, Yajun E; Oton, Ana B; Nair, Radhika

    2017-06-01

    In lung cancer, there is an increasing number of oral agents available for patients; however, little is known about the factors associated with adherence to and treatment duration on oral medications in non-small cell lung cancer (NSCLC). To evaluate the clinical and demographic factors associated with adherence and treatment discontinuation, respectively, to oral oncolytics among patients with NSCLC. A retrospective, claims-based analysis of the Humana Research Database supplemented with medical chart review was conducted among patients with NSCLC who started an oral oncolytic between January 1, 2008, and June 30, 2013. Patients were required to be enrolled at least 1 year before the start of oral oncolytics and have no evidence of any oral oncolytic use during this period. Logistic regression models and Cox proportional hazard models were used to identify predictors associated with medication adherence and treatment duration, respectively. Among all oral oncolytics, only the cohort starting on erlotinib had sufficient sample size (n = 1,452). A wide variety of factors were found to be associated with adherence. Low-income subsidy status, previous use of intravenous chemotherapy, and lower total baseline health care costs were significantly related to decreasing adherence (each P cost was associated with decreasing adherence to erlotinib (P costs (P Company to Comprehensive Health Insights, a Humana company, as a collaborative research project involving employees of both companies. Hess, Winfree, Zhu, and Oton are employees of Eli Lilly and Company. Louder and Nair are employees of Comprehensive Health Insights, which received funding to complete this research. Study concept and design were contributed by Hess, Zhu, Winfree, and Oton. Nair and Louder collected the data, and data interpretation was performed by all the authors. The manuscript was written primarily by Hess, along with Nair, and revised by Hess, Nair, Louder, and Winfree, with assistance from Zhu and

  20. Phase I Study of Conformal Radiotherapy and Concurrent Full-Dose Gemcitabine With Erlotinib for Unresected Pancreatic Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Robertson, John M., E-mail: jrobertson@beaumont.edu [Department of Radiation Oncology, William Beaumont Hospital, Royal Oak, MI (United States); Margolis, Jeffrey [Division of Medical Oncology, William Beaumont Hospital, Royal Oak, MI (United States); Jury, Robert P. [Department of Surgery, William Beaumont Hospital, Royal Oak, MI (United States); Balaraman, Savitha; Cotant, Matthew B.; Ballouz, Samer; Boxwala, Iqbal G.; Jaiyesimi, Ishmael A.; Nadeau, Laura [Division of Medical Oncology, William Beaumont Hospital, Royal Oak, MI (United States); Hardy-Carlson, Maria [Division of Radiation Oncology, M. D. Anderson Cancer Center, Houston, TX (United States); Marvin, Kimberly S.; Wallace, Michelle; Ye Hong [Department of Radiation Oncology, William Beaumont Hospital, Royal Oak, MI (United States)

    2012-02-01

    Purpose: To determine the recommended dose of radiotherapy when combined with full-dose gemcitabine and erlotinib for unresected pancreas cancer. Methods and Materials: Patients with unresected pancreatic cancer (Zubrod performance status 0-2) were eligible for the present study. Gemcitabine was given weekly for 7 weeks (1,000 mg/m{sup 2}) with erlotinib daily for 8 weeks (100 mg). A final toxicity assessment was performed in Week 9. Radiotherapy (starting at 30 Gy in 2-Gy fractions, 5 d/wk) was given to the gross tumor plus a 1-cm margin starting with the first dose of gemcitabine. A standard 3 plus 3 dose escalation (an additional 4 Gy within 2 days for each dose level) was used, except for the starting dose level, which was scheduled to contain 6 patients. In general, Grade 3 or greater gastrointestinal toxicity was considered a dose-limiting toxicity, except for Grade 3 anorexia or Grade 3 fatigue alone. Results: A total of 20 patients were treated (10 men and 10 women). Nausea, vomiting, and infection were significantly associated with the radiation dose (p = .01, p = .03, and p = .03, respectively). Of the 20 patients, 5 did not complete treatment and were not evaluable for dose-escalation purposes (3 who developed progressive disease during treatment and 2 who electively discontinued it). Dose-limiting toxicity occurred in none of 6 patients at 30 Gy, 2 of 6 at 34 Gy, and 1 of 3 patients at 38 Gy. Conclusion: The results of the present study have indicated that the recommended Phase II dose is 30 Gy in 15 fractions.

  1. Quantitative proteomics as a tool to identify resistance mechanisms in erlotinib-resistant subclones of the non-small cell lung cancer cell line HCC827

    DEFF Research Database (Denmark)

    Jacobsen, Kirstine

    , which in 43-50% of cases are caused by a secondary mutation (T790M) in EGFR. Importantly, a majority of resistance cases are still unexplained (Lin & Bivona, 2012). Our aim is to identify novel resistance mechanisms – and potentially new drug targets - in erlotinib-resistant subclones of the NSCLC cell...... of erlotinib, and in biological triplicates on a Q-Exactive mass spectrometer. Only proteins identified with minimum 2 unique peptides and in minimum 2 of 3 replicates were accepted. Results: Importantly, the resistant clones did not acquire the T790M or other EGFR or KRAS mutations, potentiating...... the identification of novel resistance mechanisms. We identified 2875 cytoplasmic proteins present in all 4 cell lines. Of these 87, 56 and 23 are upregulated >1.5 fold; and 117, 72 and 32 are downregulated >1.5 fold, respectively, in the 3 resistant clones compared to the parental cell line. By network analysis, we...

  2. A randomized study of KRAS-guided maintenance therapy with bevacizumab, erlotinib or metronomic capecitabine after first-line induction treatment of metastatic colorectal cancer

    DEFF Research Database (Denmark)

    Hagman, H; Frödin, J-E; Berglund, Å

    2016-01-01

    without progression were eligible for randomization to mt; KRAS wild-type (wt) patients were randomized to bev ± erlo (arms wt-BE, N = 36 versus wt-B, N = 35), KRAS mutated (mut) patients were randomized to bev or metronomic cap (arms mut-B, N = 34 versus mut-C, N = 33). Primary end point was progression...... to influence the outcome of treatment with erlotinib. Metronomic cap warrants further investigation in mt strategies, given our explorative results. CLINICALTRIALSGOV: NCT01229813....

  3. Regulation of epidermal growth factor receptor signaling and erlotinib sensitivity in head and neck cancer cells by miR-7.

    Directory of Open Access Journals (Sweden)

    Felicity C Kalinowski

    Full Text Available Elevated expression and activity of the epidermal growth factor receptor (EGFR/protein kinase B (Akt signaling pathway is associated with development, progression and treatment resistance of head and neck cancer (HNC. Several studies have demonstrated that microRNA-7 (miR-7 regulates EGFR expression and Akt activity in a range of cancer cell types via its specific interaction with the EGFR mRNA 3'-untranslated region (3'-UTR. In the present study, we found that miR-7 regulated EGFR expression and Akt activity in HNC cell lines, and that this was associated with reduced growth in vitro and in vivo of cells (HN5 that were sensitive to the EGFR tyrosine kinase inhibitor (TKI erlotinib (Tarceva. miR-7 acted synergistically with erlotinib to inhibit growth of erlotinib-resistant FaDu cells, an effect associated with increased inhibition of Akt activity. Microarray analysis of HN5 and FaDu cell lines transfected with miR-7 identified a common set of downregulated miR-7 target genes, providing insight into the tumor suppressor function of miR-7. Furthermore, we identified several target miR-7 mRNAs with a putative role in the sensitization of FaDu cells to erlotinib. Together, these data support the coordinate regulation of Akt signaling by miR-7 in HNC cells and suggest the therapeutic potential of miR-7 alone or in combination with EGFR TKIs in this disease.

  4. A phase I, pharmacokinetic, and pharmacodynamic study of panobinostat, an HDAC inhibitor, combined with erlotinib in patients with advanced aerodigestive tract tumors.

    Science.gov (United States)

    Gray, Jhanelle E; Haura, Eric; Chiappori, Alberto; Tanvetyanon, Tawee; Williams, Charles C; Pinder-Schenck, Mary; Kish, Julie A; Kreahling, Jenny; Lush, Richard; Neuger, Anthony; Tetteh, Leticia; Akar, Angela; Zhao, Xiuhua; Schell, Michael J; Bepler, Gerold; Altiok, Soner

    2014-03-15

    Panobinostat, a histone deacetylase (HDAC) inhibitor, enhances antiproliferative activity in non-small cell lung cancer (NSCLC) cell lines when combined with erlotinib. We evaluated this combination in patients with advanced NSCLC and head and neck cancer. Eligible patients were enrolled in a 3+3 dose-escalation design to determine the maximum tolerated dose (MTD) of twice weekly panobinostat plus daily erlotinib at four planned dose levels (DL). Pharmacokinetics, blood, fat pad biopsies (FPB) for histone acetylation, and paired pre and posttherapy tumor biopsies for checkpoint kinase 1 (CHK1) expression were assessed. Of 42 enrolled patients, 33 were evaluable for efficacy. Dose-limiting toxicities were prolonged-QTc and nausea at DL3. Adverse events included fatigue and nausea (grades 1-3), and rash and anorexia (grades 1-2). Disease control rates were 54% for NSCLC (n = 26) and 43% for head and neck cancer (n = 7). Of 7 patients with NSCLC with EGF receptor (EGFR) mutations, 3 had partial response, 3 had stable disease, and 1 progressed. For EGFR-mutant versus EGFR wild-type patients, progression-free survival (PFS) was 4.7 versus 1.9 months (P = 0.43) and overall survival was 41 (estimated) versus 5.2 months (P = 0.39). Erlotinib pharmacokinetics was not significantly affected. Correlative studies confirmed panobinostat's pharmacodynamic effect in blood, FPB, and tumor samples. Low CHK1 expression levels correlated with PFS (P = 0.006) and response (P = 0.02). We determined MTD at 30 mg (panobinostat) and 100 mg (erlotinib). Further studies are needed to further explore the benefits of HDAC inhibitors in patients with EGFR-mutant NSCLC, investigate FPB as a potential surrogate source for biomarker investigations, and validate CHK1's predictive role. ©2014 AACR.

  5. Combining Whole-Brain Radiotherapy with Gefitinib/Erlotinib for Brain Metastases from Non-Small-Cell Lung Cancer: A Meta-Analysis

    Directory of Open Access Journals (Sweden)

    Mao-hua Zheng

    2016-01-01

    Full Text Available Background. To comprehensively assess the efficacy and safety of whole-brain radiotherapy (WBRT combined with gefitinib/erlotinib for treatment of brain metastases (BM from non-small-cell lung cancer (NSCLC. Methods. Databases including PubMed, EMBASE.com, Web of Science, and Cochrane Library were searched from inception to April 12, 2015. Studies on randomized controlled trials (RCTs and case-control trials comparing WBRT combined with gefitinib/erlotinib versus WBRT alone for BM from NSCLC were included. Literature selection, data extraction, and quality assessment were performed independently by two trained reviewers. RevMan 5.3 software was used to analyze data. Results. A total of 7 trials involving 622 patients were included. Compared with WBRT alone or WBRT plus chemotherapy, WBRT plus gefitinib/erlotinib could significantly improve response rate (OR = 2.16, 95% CI: 1.35–3.47; P=0.001, remission rate of central nervous system (OR = 6.06, 95% CI: 2.57–14.29; P<0.0001, disease control rate (OR = 3.34, 95% CI: 1.84–6.07; P<0.0001, overall survival (HR = 0.72, 95% CI: 0.58–0.89; P=0.002, and 1-year survival rate (OR = 2.43, 95% CI: 1.51–3.91; P=0.0002. In adverse events (III-IV, statistically significant differences were not found, except for rash (OR = 7.96, 95% CI: 2.02–31.34; P=0.003 and myelosuppression (OR = 0.19, 95% CI: 0.07–0.51; P=0.0010. Conclusions. WBRT plus gefitinib/erlotinib was superior to WBRT alone and well tolerated in patients with BM from NSCLC.

  6. Complete response in gallbladder cancer to erlotinib plus gemcitabine does not require mutation of the epidermal growth factor receptor gene: a case report

    Directory of Open Access Journals (Sweden)

    Lincer Robert

    2010-10-01

    Full Text Available Abstract Background Gallbladder cancer typically follows an aggressive course, with chemotherapy the standard of care for advanced disease; complete remissions are rarely encountered. The epidermal growth factor receptor (EGFR is a promising therapeutic target but the activity of single agent oral EGFR tyrosine kinase inhibitors is low. There have been no previous reports of chemotherapy plus an EGFR-tyrosine kinase inhibitor (TKI to treat gallbladder cancer or correlations of response with the mutation status of the tyrosine kinase domain of the EGFR gene. Case presentation A 67 year old man with metastatic gallbladder cancer involving the liver and abdominal lymph nodes was treated with gemcitabine (1000 mg/m2 on day 1 and 8 every 21 days as well as daily erlotinib (100 mg. After four cycles of therapy, the CA 19-9 normalized and a PET/CT showed a complete remission; this response was maintained by the end of 12 cycles of therapy. Gemcitabine was then discontinued and single agent erlotinib was continued as maintenance therapy. The disease remains in good control 18 months after initiation of therapy, including 6 months on maintenance erlotinib. The only grade 3 toxicity was a typical EGFR-related skin rash. Because of the remarkable response to erlotinib plus gemcitabine, we performed tumor genotyping of the EGFR gene for response predicting mutations in exons 18, 19 and 21. This disclosed the wild-type genotype with no mutations found. Conclusion This case report demonstrates a patient with stage IV gallbladder cancer who experienced a rarely encountered complete, prolonged response after treatment with an oral EGFR-TKI plus chemotherapy. This response occurred in the absence of an EGFR gene mutation. These observations should inform the design of clinical trials using EGFR-TKIs to treat gallbladder and other biliary tract cancers; such trials should not select patients based on EGFR mutation status.

  7. Complete response in gallbladder cancer to erlotinib plus gemcitabine does not require mutation of the epidermal growth factor receptor gene: a case report

    International Nuclear Information System (INIS)

    Mody, Kabir; Strauss, Edward; Lincer, Robert; Frank, Richard C

    2010-01-01

    Gallbladder cancer typically follows an aggressive course, with chemotherapy the standard of care for advanced disease; complete remissions are rarely encountered. The epidermal growth factor receptor (EGFR) is a promising therapeutic target but the activity of single agent oral EGFR tyrosine kinase inhibitors is low. There have been no previous reports of chemotherapy plus an EGFR-tyrosine kinase inhibitor (TKI) to treat gallbladder cancer or correlations of response with the mutation status of the tyrosine kinase domain of the EGFR gene. A 67 year old man with metastatic gallbladder cancer involving the liver and abdominal lymph nodes was treated with gemcitabine (1000 mg/m2) on day 1 and 8 every 21 days as well as daily erlotinib (100 mg). After four cycles of therapy, the CA 19-9 normalized and a PET/CT showed a complete remission; this response was maintained by the end of 12 cycles of therapy. Gemcitabine was then discontinued and single agent erlotinib was continued as maintenance therapy. The disease remains in good control 18 months after initiation of therapy, including 6 months on maintenance erlotinib. The only grade 3 toxicity was a typical EGFR-related skin rash. Because of the remarkable response to erlotinib plus gemcitabine, we performed tumor genotyping of the EGFR gene for response predicting mutations in exons 18, 19 and 21. This disclosed the wild-type genotype with no mutations found. This case report demonstrates a patient with stage IV gallbladder cancer who experienced a rarely encountered complete, prolonged response after treatment with an oral EGFR-TKI plus chemotherapy. This response occurred in the absence of an EGFR gene mutation. These observations should inform the design of clinical trials using EGFR-TKIs to treat gallbladder and other biliary tract cancers; such trials should not select patients based on EGFR mutation status

  8. Complete response in gallbladder cancer to erlotinib plus gemcitabine does not require mutation of the epidermal growth factor receptor gene: a case report.

    Science.gov (United States)

    Mody, Kabir; Strauss, Edward; Lincer, Robert; Frank, Richard C

    2010-10-20

    Gallbladder cancer typically follows an aggressive course, with chemotherapy the standard of care for advanced disease; complete remissions are rarely encountered. The epidermal growth factor receptor (EGFR) is a promising therapeutic target but the activity of single agent oral EGFR tyrosine kinase inhibitors is low. There have been no previous reports of chemotherapy plus an EGFR-tyrosine kinase inhibitor (TKI) to treat gallbladder cancer or correlations of response with the mutation status of the tyrosine kinase domain of the EGFR gene. A 67 year old man with metastatic gallbladder cancer involving the liver and abdominal lymph nodes was treated with gemcitabine (1000 mg/m2) on day 1 and 8 every 21 days as well as daily erlotinib (100 mg). After four cycles of therapy, the CA 19-9 normalized and a PET/CT showed a complete remission; this response was maintained by the end of 12 cycles of therapy. Gemcitabine was then discontinued and single agent erlotinib was continued as maintenance therapy. The disease remains in good control 18 months after initiation of therapy, including 6 months on maintenance erlotinib. The only grade 3 toxicity was a typical EGFR-related skin rash. Because of the remarkable response to erlotinib plus gemcitabine, we performed tumor genotyping of the EGFR gene for response predicting mutations in exons 18, 19 and 21. This disclosed the wild-type genotype with no mutations found. This case report demonstrates a patient with stage IV gallbladder cancer who experienced a rarely encountered complete, prolonged response after treatment with an oral EGFR-TKI plus chemotherapy. This response occurred in the absence of an EGFR gene mutation. These observations should inform the design of clinical trials using EGFR-TKIs to treat gallbladder and other biliary tract cancers; such trials should not select patients based on EGFR mutation status.

  9. Synergistic effect of pacritinib with erlotinib on JAK2-mediated resistance in epidermal gowth factor receptor mutation-positive non-small cell lung Cancer.

    Science.gov (United States)

    Ochi, Nobuaki; Isozaki, Hideko; Takeyama, Masami; Singer, Jack W; Yamane, Hiromichi; Honda, Yoshihiro; Kiura, Katsuyuki; Takigawa, Nagio

    2016-06-10

    The combination effect of pacritinib, a novel JAK2/FLT3 inhibitor, with erlotinib, the epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI), on non-small cell lung cancer cells with EGFR activating mutations was investigated. The combination showed synergistic effects on JAK2-mediated EGFR TKI-resistant PC-9/ER3 cells in some cases. The combination markedly suppressed pAKT and pERK although pSTAT3 expression was similar regardless of treatment with the pacritinib, pacritinib + erlotinib, or control in PC-9/ER3 cells. Receptor tyrosine kinase array profiling demonstrated that pacritinib suppressed MET in the PC-9/ER3 cells. The combined treatment of pacritinib and erlotinib in PC-9/ER3 xenografts showed more tumor shrinkage compared with each drug as monotherapy. Western blotting revealed that pMET in tumor samples was inhibited. These results suggest MET suppression by pacritinib may play a role in overcoming the EGFR-TKI resistance mediated by JAK2 in the PC-9/ER3 cells. In conclusion, pacritinib combined with EGFR-TKI might be a potent strategy against JAK2-mediated EGFR-TKI resistance. Copyright © 2016 Elsevier Inc. All rights reserved.

  10. Network meta-analysis of erlotinib, gefitinib, afatinib and icotinib in patients with advanced non-small-cell lung cancer harboring EGFR mutations.

    Directory of Open Access Journals (Sweden)

    Wenhua Liang

    Full Text Available Several EGFR-tyrosine kinase inhibitors (EGFR-TKIs including erlotinib, gefitinib, afatinib and icotinib are currently available as treatment for patients with advanced non-small-cell lung cancer (NSCLC who harbor EGFR mutations. However, no head to head trials between these TKIs in mutated populations have been reported, which provides room for indirect and integrated comparisons.We searched electronic databases for eligible literatures. Pooled data on objective response rate (ORR, progression free survival (PFS, overall survival (OS were calculated. Appropriate networks for different outcomes were established to incorporate all evidences. Multiple-treatments comparisons (MTCs based on Bayesian network integrated the efficacy and specific toxicities of all included treatments.Twelve phase III RCTs that investigated EGFR-TKIs involving 1821 participants with EGFR mutation were included. For mutant patients, the weighted pooled ORR and 1-year PFS of EGFR-TKIs were significant superior to that of standard chemotherapy (ORR: 66.6% vs. 30.9%, OR 5.46, 95%CI 3.59 to 8.30, P<0.00001; 1-year PFS: 42.9% vs. 9.7%, OR 7.83, 95%CI 4.50 to 13.61; P<0.00001 through direct meta-analysis. In the network meta-analyses, no statistically significant differences in efficacy were found between these four TKIs with respect to all outcome measures. Trend analyses of rank probabilities revealed that the cumulative probabilities of being the most efficacious treatments were (ORR, 1-year PFS, 1-year OS, 2-year OS: erlotinib (51%, 38%, 14%, 19%, gefitinib (1%, 6%, 5%, 16%, afatinib (29%, 27%, 30%, 27% and icotinib (19%, 29%, NA, NA, respectively. However, afatinib and erlotinib showed significant severer rash and diarrhea compared with gefitinib and icotinib.The current study indicated that erlotinib, gefitinib, afatinib and icotinib shared equivalent efficacy but presented different efficacy-toxicity pattern for EGFR-mutated patients. Erlotinib and afatinib revealed

  11. Non-Targeted Metabolomics Analysis of the Effects of Tyrosine Kinase Inhibitors Sunitinib and Erlotinib on Heart, Muscle, Liver and Serum Metabolism In Vivo

    Directory of Open Access Journals (Sweden)

    Brian C. Jensen

    2017-06-01

    Full Text Available Background: More than 90 tyrosine kinases have been implicated in the pathogenesis of malignant transformation and tumor angiogenesis. Tyrosine kinase inhibitors (TKIs have emerged as effective therapies in treating cancer by exploiting this kinase dependency. The TKI erlotinib targets the epidermal growth factor receptor (EGFR, whereas sunitinib targets primarily vascular endothelial growth factor receptor (VEGFR and platelet-derived growth factor receptor (PDGFR.TKIs that impact the function of non-malignant cells and have on- and off-target toxicities, including cardiotoxicities. Cardiotoxicity is very rare in patients treated with erlotinib, but considerably more common after sunitinib treatment. We hypothesized that the deleterious effects of TKIs on the heart were related to their impact on cardiac metabolism. Methods: Female FVB/N mice (10/group were treated with therapeutic doses of sunitinib (40 mg/kg, erlotinib (50 mg/kg, or vehicle daily for two weeks. Echocardiographic assessment of the heart in vivo was performed at baseline and on Day 14. Heart, skeletal muscle, liver and serum were flash frozen and prepped for non-targeted GC-MS metabolomics analysis. Results: Compared to vehicle-treated controls, sunitinib-treated mice had significant decreases in systolic function, whereas erlotinib-treated mice did not. Non-targeted metabolomics analysis of heart identified significant decreases in docosahexaenoic acid (DHA, arachidonic acid (AA/ eicosapentaenoic acid (EPA, O-phosphocolamine, and 6-hydroxynicotinic acid after sunitinib treatment. DHA was significantly decreased in skeletal muscle (quadriceps femoris, while elevated cholesterol was identified in liver and elevated ethanolamine identified in serum. In contrast, erlotinib affected only one metabolite (spermidine significantly increased. Conclusions: Mice treated with sunitinib exhibited systolic dysfunction within two weeks, with significantly lower heart and skeletal muscle

  12. A multi species evaluation of the radiation dosimetry of [11C]erlotinib, the radiolabeled analog of a clinically utilized tyrosine kinase inhibitor

    International Nuclear Information System (INIS)

    Petrulli, J. Ryan; Hansen, Søren B.; Abourbeh, Galith; Yaqub, Maqsood; Bahce, Idris; Holden, Daniel; Huang, Yiyun; Nabulsi, Nabeel B.; Contessa, Joseph N.; Mishani, Eyal; Lammertsma, Adriaan A.; Morris, Evan D.

    2017-01-01

    Introduction: Erlotinib is a tyrosine kinase inhibitor prescribed for non-small cell lung cancer (NSCLC) patients bearing epidermal growth factor receptor mutations in the kinase domain. The objectives of this study were to (1) establish a human dosimetry profile of [ 11 C]erlotinib and (2) assess the consistency of calculated equivalent dose across species using the same dosimetry model. Methods: Subjects examined in this multi-species study included: a stage IIIa NSCLC patient, 3 rhesus macaque monkeys, a landrace pig, and 4 athymic nude-Fox1nu mice. [ 11 C]erlotinib PET data of the whole body were acquired dynamically for up to 120 min. Regions of interest (ROIs) were manually drawn to extract PET time activity curves (TACs) from identifiable organs. TACs were used to calculate time-integrated activity coefficients (residence times) in each ROI, which were then used to calculate the equivalent dose in OLINDA. Subject data were used to predict the equivalent dose to the organs of a 73.7 kg human male. Results: In three of four species, the liver was identified as the organ receiving the highest equivalent dose (critical organ). The mean equivalent doses per unit of injected activity to the liver based on human, monkey, and mouse data were 29.4 μSv/MBq, 17.4 ± 6.0 μSv/MBq, and 5.27 ± 0.25 μSv/MBq, respectively. The critical organ based on the pig data was the gallbladder wall (20.4 μSv/MBq) but the liver received a nearly identical equivalent dose (19.5 μSv/MBq). Conclusions: (1) When designing PET studies using [ 11 C]erlotinib, the liver should be considered the critical organ. (2) In organs receiving the greatest equivalent dose, mouse data underestimated the dose in comparison to larger species. However, the effective dose of [ 11 C]erlotinib to the whole body of a 73.7 kg man was predicted with good consistency based on mice (3.14 ± 0.05 μSv/MBq) or the larger species (3.46 ± 0.25 μSv/MBq).

  13. Minocycline-Induced Hyperpigmentation in a Patient Treated with Erlotinib for Non-Small Cell Lung Adenocarcinoma

    Directory of Open Access Journals (Sweden)

    Ann T. Bell

    2017-02-01

    Full Text Available Introduction: While epidermal growth factor receptor (EGFR inhibitors have improved progression-free survival in patients with non-small cell lung cancer (NSCLC, one of the most common adverse effects is papulopustular skin eruption, which is frequently severe enough to be treated with oral minocycline or doxycycline. Case: We present a case of an 87-year-old man who developed a severe papulopustular skin eruption secondary to erlotinib therapy for NSCLC. Control of the eruption with 100 mg of minocycline twice daily for 8 months eventually led to blue-gray skin hyperpigmentation. After 30 months, this side effect was recognized as minocycline drug deposition, which was confirmed with skin biopsy. Discussion: Compliance with EGFR inhibitor therapy in NSCLC is often challenging due to common side effects, most notably cutaneous skin eruptions. Treatment of cutaneous toxicities is important to preserve patient compliance with targeted cancer therapy. Use of minocycline to treat the most common cutaneous side effect (papulopustular eruption can in turn cause blue-black skin, eye, or tooth discoloration that can nullify its benefits, resulting in suboptimal patient adherence to cancer therapy. Although this adverse effect is well known in dermatology literature as a risk when using minocycline to treat acne, rosacea, or blistering disorders, it is less well documented in oncology literature. We present this case to highlight the need for greater consideration of unique patient characteristics in selecting an oral antibiotic as a treatment modality for EGFR inhibitor skin toxicities.

  14. Effects of Cetuximab and Erlotinib on the behaviour of cancer stem cells in head and neck squamous cell carcinoma.

    Science.gov (United States)

    Setúbal Destro Rodrigues, Maria Fernanda; Gammon, Luke; Rahman, Muhammad M; Biddle, Adrian; Nunes, Fabio Daumas; Mackenzie, Ian C

    2018-03-02

    The therapeutic responses of many solid tumours to chemo- and radio-therapies are far from fully effective but therapies targeting malignancy-related cellular changes show promise for further control. In head and neck squamous cell carcinoma, the epidermal growth factor receptor (EGFR) is commonly overexpressed and investigation of agents that block this receptor indicate a limited response when used alone but an ability to enhance the actions of other drugs. The hierarchical stem cell patterns present in tumours generate cellular heterogeneity and this is further complicated by cancer stem cells (CSC) shifting between epithelial (Epi-CSC) and mesenchymal (EMT-CSC) states. To clarify how such heterogeneity influences responses to EGFR blocking, we examined the effects of Cetuximab and Erlotinib on the cell sub-populations in HNSCC cell lines. These agents reduced cell proliferation for all subpopulations but induced little cell death. They did however induce large shifts of cells between the EMT-CSC, Epi-CSC and differentiating cell compartments. Loss of EMT-CSCs reduced cell motility and is expected to reduce invasion and metastasis. EGFR blocking also induced shifts of Epi-CSCs into the differentiating cell compartment which typically has greater sensitivity to chemo/radiation, an effect expected to enhance the overall response of tumour cell populations to adjunctive therapies.

  15. Effects of Cetuximab and Erlotinib on the behaviour of cancer stem cells in head and neck squamous cell carcinoma

    Science.gov (United States)

    Setúbal Destro Rodrigues, Maria Fernanda; Gammon, Luke; Rahman, Muhammad M.; Biddle, Adrian; Nunes, Fabio Daumas; Mackenzie, Ian C.

    2018-01-01

    The therapeutic responses of many solid tumours to chemo- and radio-therapies are far from fully effective but therapies targeting malignancy-related cellular changes show promise for further control. In head and neck squamous cell carcinoma, the epidermal growth factor receptor (EGFR) is commonly overexpressed and investigation of agents that block this receptor indicate a limited response when used alone but an ability to enhance the actions of other drugs. The hierarchical stem cell patterns present in tumours generate cellular heterogeneity and this is further complicated by cancer stem cells (CSC) shifting between epithelial (Epi-CSC) and mesenchymal (EMT-CSC) states. To clarify how such heterogeneity influences responses to EGFR blocking, we examined the effects of Cetuximab and Erlotinib on the cell sub-populations in HNSCC cell lines. These agents reduced cell proliferation for all subpopulations but induced little cell death. They did however induce large shifts of cells between the EMT-CSC, Epi-CSC and differentiating cell compartments. Loss of EMT-CSCs reduced cell motility and is expected to reduce invasion and metastasis. EGFR blocking also induced shifts of Epi-CSCs into the differentiating cell compartment which typically has greater sensitivity to chemo/radiation, an effect expected to enhance the overall response of tumour cell populations to adjunctive therapies. PMID:29568372

  16. An economic analysis of erlotinib, docetaxel, pemetrexed and best supportive care as second or third line treatment of non-small cell lung cancer

    Directory of Open Access Journals (Sweden)

    A. Araújo

    2008-11-01

    Full Text Available Aim: Evaluate costs and benefits of erlotinib as 2nd or 3rd line treatment of advanced or metastatic nonsmall cell lung cancer (NSCLC versus docetaxel, pemetrexed and best supportive care. Materials and methods: Cost-minimisation and cost-utility analysis were performed. Time horizon of two years. Portuguese National Health System (NHS perspective was applied. Survival and time to progression were obtained from three clinical trials. Base-case analysis: 2nd or 3rd line patients with advanced or metastatic NSCLC. Quality Adjusted Life Years (QALYs were obtained from a UK study. Resource consumption was estimated by a Portuguese panel of experts. Costs were calculated according to official Portuguese databases (updated to 2008. Only direct health costs were applied. Annual discount rate: 5%. Sensitivity analysis included different subpopulations, a three year time horizon and a probabilistic analysis. Results: The cost per patient was lower with erlotinib (€26 478 than docetaxel (€29 262 or pemetrexed (€32 762 and higher than best supportive care (€16 112. QALYs per patient were higher with erlotinib (0.250 than docetaxel (0.225, pemetrexed (0.241 or best supportive care (0.186. Erlotinib was dominant in the cost-utility analysis, with a lower cost and a higher efficacy than docetaxel and pemetrexed. The sensitivity analysis confirmed the robustness of the base-case analysis results. Conclusions: The use of erlotinib instead of docetaxel or pemetrexed could contribute to annual savings for the NHS (substitution rates: 5%–65% ranging from €135 046-€1 755 602 (docetaxel replacement and €291 801-€3 793 409 (pemetrexed replacement, with a gain in terms of QALYs. Resumo: Objectivo: Avaliar o custo-efectividade de erlotinib na segunda ou terceira linha do tratamento do cancro do pulmão de não pequenas células (CPNPC avançado ou metastizado versus docetaxel, pemetrexedo ou tratamento de suporte

  17. Guides et formulaires | CRDI - Centre de recherches pour le ...

    International Development Research Centre (IDRC) Digital Library (Canada)

    Demande de subvention de recherche du CRDI · Budget de proposition · Lignes directrices du CRDI pour la préparation du rapport d'étape technique · Lignes directrices du CRDI pour la préparation du rapport technique final · Lignes directrices du CRDI pour les dépenses de projet admissibles · Lignes directrices pour la ...

  18. Erlotinib 150 mg daily plus chemotherapy in advanced pancreatic cancer: an interim safety analysis of a multicenter, randomized, cross-over phase III trial of the 'Arbeitsgemeinschaft Internistische Onkologie'.

    Science.gov (United States)

    Boeck, Stefan; Vehling-Kaiser, Ursula; Waldschmidt, Dirk; Kettner, Erika; Märten, Angela; Winkelmann, Cornelia; Klein, Stefan; Kojouharoff, Georgi; Gauler, Thomas; Fischer von Weikersthal, Ludwig; Clemens, Michael R; Geissler, Michael; Greten, Tim F; Hegewisch-Becker, Susanna; Neugebauer, Sascha; Heinemann, Volker

    2010-01-01

    To date, only limited toxicity data are available for the combination of erlotinib with either capecitabine or gemcitabine as front-line therapy for advanced pancreatic cancer. Within a randomized phase III trial, 281 treatment-naive patients were randomly assigned between capecitabine (2000 mg/m/day, for 14 days, once every 3 weeks) plus erlotinib (150 mg/day, arm A) and gemcitabine (1000 mg/m as a 30-min infusion) plus erlotinib (150 mg/day, arm B). In case of treatment failure, patients were crossed over to a second-line treatment with the comparator cytostatic drug without erlotinib. The primary study endpoint was the time to treatment failure of second-line therapy (TTF2). This interim analysis of toxicity contains safety data from the first 127 randomized patients. During first-line therapy, patients received a median number of three treatment cycles (range 0-13) in both the arms. Regarding chemotherapy, a treatment delay was observed in 12% of the cycles in arm A and in 22% of the cycles in arm B. Dose reductions of the cytostatic drug were performed in 18 and 27% of treatment cycles, respectively. Erlotinib dose reductions were performed in 6 and 11% of all cycles. Grade 3/4 hematological toxicity was arms; major grade 3/4 toxicities in arms A and B were diarrhea (9 vs. 7%), skin rash (4 vs. 12%), and hand-foot syndrome (7 vs. 0%). No treatment-related death was observed. In conclusion, this interim safety analysis suggests that treatment with erlotinib 150 mg/day is feasible in combination with capecitabine or gemcitabine.

  19. Penjadwalan Produksi Garment Menggunakan Algoritma Heuristic Pour

    Directory of Open Access Journals (Sweden)

    Rizal Rachman

    2018-04-01

    Full Text Available Abstrak Penjadwalan merupakan suatu kegiatan pengalokasian sumber daya yang terbatas untuk mengerjakan sejumlah pekerjaan. Proses penjadwalan timbul jika terdapat keterbatasan sumber daya yang dimiliki, karena pada saat ini perusahaan menerapkan sistem penjadwalan manual dimana dengan penjadwalan tersebut masih terdapat beberapa produk yang terlewati sehingga menyebabkan keterlambatan dalam proses produksi, aturan ini sering tidak menguntungkan bagi order yang membutuhkan waktu proses pendek karena apabila order itu berada dibelakang antrian maka harus menunggu lama sebelum diproses dan menyebabkan waktu penyelesaian seluruh order menjadi panjang, sehingga diperlukan adanya pengaturan sumber-sumber daya yang ada secara efisien. Adapun dasar perhitungan Penjadwalan dengan menggunakan algoritma Heuristic Pour. Tahapan-tahapan penelitian terdiri dari pengumpulan data, perhitungan waktu standar, perhitungan total waktu proses berdasarkan job, penjadwalan dengan metode awal perusahaan, penjadwalan dengan metode Heuristik Pour. Berdasarkan hasil penjadwalan menggunakan Heuristik Pour diperoleh penghematan dibanding dengan metode perusahaan saat ini, sehingga dapat digunakan sebagai alternatif metode dalam melakukan penjadwalan pengerjaan proses produksi di perusahaan Garment tersebut. Kata kunci: Penjadwalan Produksi, Algoritma, Heuristic Pour. Abstract Scheduling is a limited resource allocation activity to do a number of jobs. The scheduling process arises if there are limited resources available, because at this time the company implement a manual scheduling system where the scheduling is still there are some products passed so as to cause delays in the production process, this rule is often not profitable for orders that require short processing time because if the order is behind the queue then it must wait a long time before it is processed and cause the completion time of all orders to be long, so it is necessary to regulate the existing

  20. Estimating emissions from grout pouring operations

    International Nuclear Information System (INIS)

    Ballinger, M.Y.; Hendrickson, D.W.

    1993-08-01

    Grouting is a method for disposal of low-level radioactive waste in which a contaminated solution is mixed into a slurry, poured into a large storage vault, then dried, fixing the contaminants within a stable solid matrix. A model (RELEASE) has been developed to estimate the quantity of aeorsol created during the pouring process. Information and equations derived from spill experiments were used in the model to determine release fractions. This paper discusses the derivation of the release fraction equation used in the code and the model used to account for gravity settling of particles in the vault. The input and results for a base case application are shown

  1. Joint Serum Tumor Markers Serve as survival predictive model of Erlotinib in the treatment of recurrent Non-small Cell Lung Cancer

    Directory of Open Access Journals (Sweden)

    Lan SHAO

    2014-05-01

    Full Text Available Background and objective Molecular targeting therapy is the direction of individualized treatment of lung cancer, scholars has been established targeted therapy prediction models which provide more guidance for clinical individual therapy. This study investigated the relationship among pulmonary surfactant-associated protein D (SP-D, transforming growth factor α (TGF-α, matrix metalloproteinase 9 (MMP-9, tissue polypeptide specific antigen (TPS, and Krebs von den Lungen-6 (KL-6 and response as well as survival in the patients with recurrent non-small cell lung cancer, which Erlotinib was as second line treatment after failure to chemotherapy. This study also established a predictive prognostic model. Methods Serum levels of SP-D, TGF-α, MMP-9, TPS, and KL-6 in 114 patients before erlotinib treatment were detected by ELISA method. Combined with clinical factors, these levels were used to investigate the relationship with efficacy in erlotinib treatment and construct a predicted prognostic model by Kaplan-Meier curve and Cox proportional hazard model multivariate analysis. Results The objective response rate (ORR and disease control rate (DCR in the 114 patients, were 22.8% (26/114 and 72.8% (83/114, to Erlotinib treatment respectively. The median progression-free survival (PFS and one year survival rate with Erlotinib treatment were 5.13 months and 69.3%, respectively. Patients in the SP-D>110 ng/mL group exhibited more ORR (33.3% vs 13.3%, P=0.011 and DCR (83.3% vs 63.3%, P=0.017 than those in the ≤110 ng/mL group. Patients in the MMP-9≤535 ng/mL group showed more DCR (83.9% than those in the >535 ng/mL group (62.1% (P=0.009. Patients in the TPS110 ng/mL (5.95 months vs 3.25 months, P=0.009, MMP-9≤535 ng/mL (5.83 months vs 3.47 months, P=0.046, KL-6<500 U/mL (6.03 months vs 3.40 months, P=0.040, and TPS<80 U/L (6.15 months vs 2.42 months, P=0.014 groups showed better PFS. Multivariate analysis showed that current or ever-smoker, wild

  2. Tamoxifen enhances erlotinib-induced cytotoxicity through down-regulating AKT-mediated thymidine phosphorylase expression in human non-small-cell lung cancer cells.

    Science.gov (United States)

    Ko, Jen-Chung; Chiu, Hsien-Chun; Syu, Jhan-Jhang; Jian, Yi-Jun; Chen, Chien-Yu; Jian, Yun-Ting; Huang, Yi-Jhen; Wo, Ting-Yu; Lin, Yun-Wei

    2014-03-01

    Tamoxifen is a triphenylethylene nonsteroidal estrogen receptor (ER) antagonist used worldwide as an adjuvant hormone therapeutic agent in the treatment of breast cancer. However, the molecular mechanism of tamoxifen-induced cytotoxicity in non-small cell lung cancer (NSCLC) cells has not been identified. Thymidine phosphorylase (TP) is an enzyme of the pyrimidine salvage pathway which is upregulated in cancers. In this study, tamoxifen treatment inhibited cell survival in two NSCLC cells, H520 and H1975. Treatment with tamoxifen decreased TP mRNA and protein levels through AKT inactivation. Furthermore, expression of constitutively active AKT (AKT-CA) vectors significantly rescued the decreased TP protein and mRNA levels in tamoxifen-treated NSCLC cells. In contrast, combination treatment with PI3K inhibitors (LY294002 or wortmannin) and tamoxifen further decreased the TP expression and cell viability of NSCLC cells. Knocking down TP expression by transfection with small interfering RNA of TP enhanced the cytotoxicity and cell growth inhibition of tamoxifen. Erlotinib (Tarceva, OSI-774), an orally available small molecular inhibitor of epidermal growth factor receptor (EGFR) tyrosine kinase, is approved for clinical treatment of NSCLC. Compared to a single agent alone, tamoxifen combined with erlotinib resulted in cytotoxicity and cell growth inhibition synergistically in NSCLC cells, accompanied with reduced activation of phospho-AKT and phospho-ERK1/2, and reduced TP protein levels. These findings may have implications for the rational design of future drug regimens incorporating tamoxifen and erlotinib for the treatment of NSCLC. Copyright © 2014 Elsevier Inc. All rights reserved.

  3. TLG-S criteria are superior to both EORTC and PERCIST for predicting outcomes in patients with metastatic lung adenocarcinoma treated with erlotinib

    Energy Technology Data Exchange (ETDEWEB)

    Ho, Kung-Chu [National Taiwan University, Graduate Institute of Biomedical Electronics and Bioinformatics, Taipei (China); Chang Gung Memorial Hospital and Chang Gung University, Department of Nuclear Medicine and Center for Advanced Molecular Imaging and Translation, Taoyuan (China); Fang, Yu-Hua Dean [National Cheng Kung University, Department of Biomedical Engineering, Tainan (China); Chung, Hsiao-Wen [National Taiwan University, Graduate Institute of Biomedical Electronics and Bioinformatics, Taipei (China); Liu, Yuan-Chang [Chang Gung Memorial Hospital and Chang Gung University, Department of Medical Imaging and Intervention, Taoyuan (China); Chang, John Wen-Cheng; Hou, Ming-Mo [Chang Gung Memorial Hospital and Chang Gung University, Division of Hematology-Oncology, Department of Internal Medicine, Taoyuan (China); Yang, Cheng-Ta [Chang Gung Memorial Hospital and Chang Gung University, Department of Thoracic Medicine, Taoyuan (China); Cheng, Nai-Ming; Yen, Tzu-Chen [Chang Gung Memorial Hospital and Chang Gung University, Department of Nuclear Medicine and Center for Advanced Molecular Imaging and Translation, Taoyuan (China); Su, Tzu-Pei [Chang Gung Memorial Hospital, Department of Nuclear Medicine, Keelung (China)

    2016-11-15

    In this retrospective review of prospectively collected data, we sought to investigate whether early FDG-PET assessment of treatment response based on total lesion glycolysis measured using a systemic approach (TLG-S) would be superior to either local assessment with EORTC (European Organization for Research and Treatment of Cancer) criteria or single-lesion assessment with PERCIST (PET Response Criteria in Solid Tumors) for predicting clinical outcomes in patients with metastatic lung adenocarcinoma treated with erlotinib. We also examined the effect of bone flares on tumor response evaluation by single-lesion assessment with PERCIST in patients with metastatic bone lesions. We performed a retrospective review of prospectively collected data from 23 patients with metastatic lung adenocarcinoma treated with erlotinib. All participants underwent FDG-PET imaging at baseline and on days 14 and 56 after completion of erlotinib treatment. In addition, diagnostic CT scans were performed at baseline and on day 56. FDG-PET response was assessed with TLG-S, EORTC, and PERCIST criteria. Response assessment based on RECIST 1.1 (Response Evaluation Criteria in Solid Tumors) from diagnostic CT imaging was used as the reference standard. Two-year progression-free survival (PFS) and overall survival (OS) served as the main outcome measures. We identified 13 patients with bone metastases. Of these, four (31 %) with persistent bone uptake due to bone flares on day 14 were erroneously classified as non-responders according to the PERCIST criteria, but they were correctly classified as responders according to both the EORTC and TLG-S criteria. Patients who were classified as responders on day 14 based on TLG-S criteria had higher rates of 2-year PFS (26.7 % vs. 0 %, P = 0.007) and OS (40.0 % vs. 7.7 %, P = 0.018). Similar rates were observed in patients who showed a response on day 56 based on CT imaging according to the RECIST criteria. Patients classified as responders on day 14

  4. Preliminary analysis of the risk factors for radiation pneumonitis in patients with non- small-cell lung cancer treated with concurrent erlotinib and thoracic radiotherapy

    Directory of Open Access Journals (Sweden)

    Zhuang H

    2014-05-01

    Full Text Available Hongqing Zhuang,* Hailing Hou,* Zhiyong Yuan, Jun Wang, Qingsong Pang, Lujun Zhao, Ping WangDepartment of Radiotherapy, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tianjin Key Laboratory of Cancer Prevention and Therapy, and Tianjin Lung Cancer Center, Tianjin, People's Republic of China*These authors contributed equally to this workPurpose: The aim of this study was to investigate radiation pneumonitis and its associated risk factors in patients with non-small-cell lung cancer treated with concurrent erlotinib and thoracic radiotherapy.Materials and methods: We conducted an analysis of patients with nonoperable stage IIIA–IV non-small-cell lung cancer who were treated with concurrent thoracic radiotherapy and erlotinib (ClinicalTrials.gov identifier: NCT00973310. The Common Terminology Criteria for Adverse Events version 3.0 grading system was applied to evaluate the incidence of radiation pneumonitis. The lung dosimetric parameters were recorded in accordance with the treatment plan, and the study endpoint was radiation pneumonitis at grade 2 or more.Results: Among the 24 selected clinical cases, nine were identified with radiation pneumonitis of grade 2 or above (37.5%. This included four cases with grade 2 (16.7%, two cases with grade 3 (8.3%, and three cases with grade 5 (12.5%. The results showed that the planning target volume was a significant factor affecting the incidence of radiation pneumonitis. All lung dosimetric parameters exhibited statistically significant differences between patients with pneumonitis and patients without pneumonitis. The receiver operating characteristic (ROC curve analysis showed that all lung dosimetric parameters were useful in predicting the incidence of radiation pneumonitis. In addition, the threshold values of V5, V10, V15, V20, V30, and mean lung dose were >4%, >29%, >27%, >22%, >17% and >1,027 cGy, respectively.Conclusion: Special attention

  5. Focal Adhesion Kinase Inhibitors in Combination with Erlotinib Demonstrate Enhanced Anti-Tumor Activity in Non-Small Cell Lung Cancer.

    Directory of Open Access Journals (Sweden)

    Grant A Howe

    Full Text Available Blockade of epidermal growth factor receptor (EGFR activity has been a primary therapeutic target for non-small cell lung cancers (NSCLC. As patients with wild-type EGFR have demonstrated only modest benefit from EGFR tyrosine kinase inhibitors (TKIs, there is a need for additional therapeutic approaches in patients with wild-type EGFR. As a key component of downstream integrin signalling and known receptor cross-talk with EGFR, we hypothesized that targeting focal adhesion kinase (FAK activity, which has also been shown to correlate with aggressive stage in NSCLC, would lead to enhanced activity of EGFR TKIs. As such, EGFR TKI-resistant NSCLC cells (A549, H1299, H1975 were treated with the EGFR TKI erlotinib and FAK inhibitors (PF-573,228 or PF-562,271 both as single agents and in combination. We determined cell viability, apoptosis and 3-dimensional growth in vitro and assessed tumor growth in vivo. Treatment of EGFR TKI-resistant NSCLC cells with FAK inhibitor alone effectively inhibited cell viability in all cell lines tested; however, its use in combination with the EGFR TKI erlotinib was more effective at reducing cell viability than either treatment alone when tested in both 2- and 3-dimensional assays in vitro, with enhanced benefit seen in A549 cells. This increased efficacy may be due in part to the observed inhibition of Akt phosphorylation when the drugs were used in combination, where again A549 cells demonstrated the most inhibition following treatment with the drug combination. Combining erlotinib with FAK inhibitor was also potent in vivo as evidenced by reduced tumor growth in the A549 mouse xenograft model. We further ascertained that the enhanced sensitivity was irrespective of the LKB1 mutational status. In summary, we demonstrate the effectiveness of combining erlotinib and FAK inhibitors for use in known EGFR wild-type, EGFR TKI resistant cells, with the potential that a subset of cell types, which includes A549, could be

  6. De meilleurs emplois pour l'Asie

    International Development Research Centre (IDRC) Digital Library (Canada)

    Offrir de meilleurs emplois en Asie exigera des interventions créatives de la part des gouvernements, des employeurs et des entrepreneurs. Le CRDI aide les établisse- ments de recherche à trouver des .... de dollars en 2014, ont entraîné une expansion majeure des emplois pour les. Bangladaises. On s'attend à ce que ...

  7. Phase 1 trial of the oral AKT inhibitor MK-2206 plus carboplatin/paclitaxel, docetaxel, or erlotinib in patients with advanced solid tumors.

    Science.gov (United States)

    Molife, L Rhoda; Yan, Li; Vitfell-Rasmussen, Joanna; Zernhelt, Adriane M; Sullivan, Daniel M; Cassier, Philippe A; Chen, Eric; Biondo, Andrea; Tetteh, Ernestina; Siu, Lillian L; Patnaik, Amita; Papadopoulos, Kyriakos P; de Bono, Johann S; Tolcher, Anthony W; Minton, Susan

    2014-01-03

    Inhibition of AKT with MK-2206 has demonstrated synergism with anticancer agents. This phase 1 study assessed the MTD, DLTs, PK, and efficacy of MK-2206 in combination with cytotoxic and targeted therapies. Advanced solid tumor patients received oral MK-2206 45 or 60 mg (QOD) with either carboplatin (AUC 6.0) and paclitaxel 200 mg/m2 (arm 1), docetaxel 75 mg/m2 (arm 2), or erlotinib 100 or 150 mg daily (arm 3); alternative schedules of MK-2206 135-200 mg QW or 90-250 mg Q3W were also tested. MTD of MK-2206 (N = 72) was 45 mg QOD or 200 mg Q3W (arm 1); MAD was 200 mg Q3W (arm 2) and 135 mg QW (arm 3). DLTs included skin rash (arms 1, 3), febrile neutropenia (QOD, arms 1, 2), tinnitus (Q3W, arm 2), and stomatitis (QOD, arm 3). Common drug-related toxicities included fatigue (68%), nausea (49%), and rash (47%). Two patients with squamous cell carcinoma of the head and neck (arm 1; Q3W) demonstrated a complete and partial response (PR); additional PRs were observed in patients (1 each) with melanoma, endometrial, neuroendocrine prostate, NSCLC, and cervical cancers. Six patients had stable disease ≥6 months. MK-2206 plus carboplatin and paclitaxel, docetaxel, or erlotinib was well-tolerated, with early evidence of antitumor activity.

  8. Pitié pour les grandes villes !

    Directory of Open Access Journals (Sweden)

    Jérôme Monnet

    1997-02-01

    Full Text Available Roger Caillois disait, en 1938, qu´il existe "une représentation de la grande ville, assez puissante sur les imaginations pour que jamais en pratique ne soit posée la question de son exactitude, créée de toute pièce par le livre, assez répandue néanmoins pour faire partie de l´atmosphère mentale collective et posséder par suite une certaine force de contrainte"(Le mythe et l´homme, p.156 [c´est lui qui souligne]. En 1996, la presse française a consacré dossiers et articles à "Habitat II...

  9. A randomized, double-blind, phase III study comparing two doses of erlotinib for second-line treatment of current smokers with advanced non-small-cell lung cancer (CurrentS).

    Science.gov (United States)

    Smit, Egbert F; Wu, Yi-Long; Gervais, Radj; Zhou, Caicun; Felip, Enriqueta; Feng, Jifeng; Guclu, Salih Zeki; Hoiczyk, Mathias; Dorokhova, Elena; Freudensprung, Ulrich; Grange, Susan; Perez-Moreno, Pablo Diego; Mitchell, Lada; Reck, Martin

    2016-09-01

    Active smokers with non-small-cell lung cancer (NSCLC) have increased erlotinib metabolism versus non-smoking patients, which reduces exposure. Therefore, an increased erlotinib dose may be beneficial. The CurrentS study (NCT01183858) assessed efficacy and safety of 300mg erlotinib (E300) as second-line therapy in current smokers with locally advanced or metastatic NSCLC versus the standard 150mg dose (E150). Patients with stage IIIB/IV NSCLC (current smokers who failed first-line platinum-based chemotherapy) were randomized to receive E150 or E300 until progression/death/unacceptable toxicity. progression-free survival (PFS). Secondary endpoints: overall survival (OS), disease control rate and safety. A total of 342 patients were screened; the intent-to-treat population comprised 159 E300 patients and 154 E150 patients. Median PFS was 7.0 versus 6.9 weeks with E300 versus E150, respectively (unstratified hazard ratio [HR]=1.05, 95% confidence interval [CI]: 0.83-1.33; unstratified log-rank P=0.671). Median OS was 6.8 months in both arms (unstratified HR=1.03, 95% CI: 0.80-1.32; unstratified log-rank P=0.846). Overall, 89.2% (E300 arm) and 84.4% (E150 arm) experienced ≥1 adverse event (AE) of any grade (44.3% and 37%, respectively, experienced grade ≥3 AEs); AEs of special interest were reported in 67.7% and 47.4% of patients, respectively. E300 resulted in higher mean plasma concentrations versus E150, however, this did not improve efficacy. Despite the difference in erlotinib exposure, there was no evidence of an incremental efficacy benefit of a higher erlotinib dose versus the standard dose in this population of highly active smokers. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  10. Plutonium Immobilization Program cold pour tests

    International Nuclear Information System (INIS)

    Hovis, G.L.; Stokes, M.W.; Smith, M.E.; Wong, J.W.

    1999-01-01

    The Plutonium Immobilization Program (PIP) is a joint venture between the Savannah River Site, Lawrence Livermore National Laboratory, Argonne National Laboratory, and Pacific Northwest National Laboratory to carry out the disposition of excess weapons-grade plutonium. This program uses the can-in-canister (CIC) approach. CIC involves encapsulating plutonium in ceramic forms (or pucks), placing the pucks in sealed stainless steel cans, placing the cans in long cylindrical magazines, latching the magazines to racks inside Defense Waste Processing Facility (DWPF) canisters, and filling the DWPF canisters with high-level waste glass. This process puts the plutonium in a stable form and makes it attractive for reuse. At present, the DWPF pours glass into empty canisters. In the CIC approach, the addition of a stainless steel rack, magazines, cans, and ceramic pucks to the canisters introduces a new set of design and operational challenges: All of the hardware installed in the canisters must maintain structural integrity at elevated (molten-glass) temperatures. This suggests that a robust design is needed. However, the amount of material added to the DWPF canister must be minimized to prevent premature glass cooling and excessive voiding caused by a large internal thermal mass. High metal temperatures, minimizing thermal mass, and glass flow paths are examples of the types of technical considerations of the equipment design process. To determine the effectiveness of the design in terms of structural integrity and glass-flow characteristics, full-scale testing will be conducted. A cold (nonradioactive) pour test program is planned to assist in the development and verification of a baseline design for the immobilization canister to be used in the PIP process. The baseline design resulting from the cold pour test program and CIC equipment development program will provide input to Title 1 design for second-stage immobilization. The cold pour tests will be conducted in two

  11. A Statistical Treatment of Bioassay Pour Fractions

    Science.gov (United States)

    Barengoltz, Jack; Hughes, David W.

    2014-01-01

    The binomial probability distribution is used to treat the statistics of a microbiological sample that is split into two parts, with only one part evaluated for spore count. One wishes to estimate the total number of spores in the sample based on the counts obtained from the part that is evaluated (pour fraction). Formally, the binomial distribution is recharacterized as a function of the observed counts (successes), with the total number (trials) an unknown. The pour fraction is the probability of success per spore (trial). This distribution must be renormalized in terms of the total number. Finally, the new renormalized distribution is integrated and mathematically inverted to yield the maximum estimate of the total number as a function of a desired level of confidence ( P(fraction. The extension to recovery efficiency corrections is also presented. Now the product of recovery efficiency and pour fraction may be small enough that the likely value may be much larger than the usual calculation: the number of spores divided by that product. The use of this analysis would not be limited to microbiological data.

  12. Myanmar : tous les projets | CRDI - Centre de recherches pour le ...

    International Development Research Centre (IDRC) Digital Library (Canada)

    Programme: Governance and Justice ... La création de zones économiques frontalières constitue une importante stratégie d'industrialisation pour la Thaïlande et ouvre de nouvelles perspectives pour deux ... Una Hakika : Porter à grande échelle les solutions numériques pour la gestion des conflits au Kenya et en Birmanie.

  13. Inde | Page 77 | CRDI - Centre de recherches pour le ...

    International Development Research Centre (IDRC) Digital Library (Canada)

    Ce n'est un secret pour personne que les produits agricoles traditionnels comme les mils et les légumineuses à graines sont très nutritifs. C'est pourquoi des chercheurs collaborent actuellement avec des femmes en Inde et en Éthiopie pour faciliter l'utilisation à des fins personnelles (pour la préparation de repas sains) et ...

  14. The effect of pouring time on the dimensional stability of casts made from conventional and extended-pour irreversible hydrocolloids by 3D modelling

    Directory of Open Access Journals (Sweden)

    Hasan Ö. Gümüş

    2015-09-01

    Conclusion: All of the conventional and extended-pour impression materials tested in this study can be poured up to 24 hours with accuracy, if impressions are correctly stored. Extended-pour impression materials (ColorChange, Hydrogum 5, and Hydrocolor 5 can be poured up to 120 hours, if stored correctly.

  15. Prognostic impact of initial maximum standardized uptake value of 18F-FDG PET/CT on treatment response in patients with metastatic lung adenocarcinoma treated with erlotinib

    Directory of Open Access Journals (Sweden)

    Kus T

    2015-12-01

    Full Text Available Tulay Kus,1 Gokmen Aktas,1 Alper Sevinc,1 Mehmet Emin Kalender,1 Mustafa Yilmaz,2 Seval Kul,3 Serdar Oztuzcu,4 Cemil Oktay,5 Celaletdin Camci1 1Department of Internal Medicine, Division of Medical Oncology, Gaziantep Oncology Hospital, 2Department of Nuclear Medicine, 3Department of Biostatistics, Faculty of Medicine, 4Department of Medical Biology, Faculty of Medicine, University of Gaziantep, Gaziantep, 5Department of Radiology, Faculty of Medicine, University of Akdeniz, Antalya, Turkey Purpose: To investigate whether the initial maximum standardized uptake value (SUVmax on fluorine-18 fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT has a prognostic significance in metastatic lung adenocarcinoma.Patients and methods: Sixty patients (24 females, mean age: 57.9±12 years with metastatic stage lung adenocarcinoma who used erlotinib and underwent 18F-FDG PET/CT at the time of diagnosis between May 2010 and May 2014 were enrolled in this retrospective study. The patients were stratified according to the median SUVmax value, which was found as 11. Progression-free survival (PFS rates for 3, 6, and 12 months were examined for SUVmax values and epidermal growth factor receptor (EGFR mutation status.Results: The number of EGFR-sensitizing mutation positive/negative/unknown was 26/17/17, respectively, and the number of patients using erlotinib at first-line, second-line, and third-line therapy was 15, 31, and 14 consecutively. The PFS rates of EGFR mutation positive, negative, and unknown patients for 3 months were 73.1%, 35.3%, and 41.2% (P=0.026, odds ratio [OR]=4.39; 95% confidence interval [CI]: 1.45–13.26, respectively. The PFS rates of EGFR positive, negative, and unknown patients for 6 months were 50%, 29.4%, and 29.4% (P=0.267, OR: 2.4; 95% CI: 0.82–6.96, respectively. The PFS rates of EGFR positive, negative, and unknown patients for 12 months were 42.3%, 29.4%, 23.5% (P=0.408, OR: 2.0; 95% CI: 0.42

  16. Afatinib versus erlotinib as second-line treatment of patients with advanced squamous cell carcinoma of the lung (LUX-Lung 8)

    DEFF Research Database (Denmark)

    Soria, Jean-Charles; Felip, Enriqueta; Cobo, Manuel

    2015-01-01

    BACKGROUND: There is a major unmet need for effective treatments in patients with squamous cell carcinoma of the lung. LUX-Lung 8 compared afatinib (an irreversible ErbB family blocker) with erlotinib (a reversible EGFR tyrosine kinase inhibitor), as second-line treatment for patients with advanced...... squamous cell carcinoma of the lung. METHODS: We did this open-label, phase 3 randomised controlled trial at 183 cancer centres in 23 countries worldwide. We enrolled adults with stage IIIB or IV squamous cell carcinoma of the lung who had progressed after at least four cycles of platinum...... be an additional option for the treatment of patients with squamous cell carcinoma of the lung. FUNDING: Boehringer Ingelheim....

  17. 21 conseils pour la collecte de fonds

    International Development Research Centre (IDRC) Digital Library (Canada)

    Visite. Comme ils ne prendront pas la peine de répondre aux lettres qui leur sont adressées (ou aux messages par télécopie, ou aux appels téléphoniques), vous devez vous rendre auprès d'eux. Il faudra plusieurs messages par télécopieur ou appels téléphoniques pour obtenir un rendez-vous. Toutefois, s'ils savent que ...

  18. Changements climatiques | CRDI - Centre de recherches pour le ...

    International Development Research Centre (IDRC) Digital Library (Canada)

    L'objectif du programme Changements climatiques consiste à appuyer des partenariats et des réseaux visant à rassembler des données probantes pour trouver des solutions et utiliser les technologies en vue d'obtenir des gains sociaux et économiques et d'atténuer les effets des changements climatiques pour l'avenir.

  19. Villes durables intelligentes | CRDI - Centre de recherches pour le ...

    International Development Research Centre (IDRC) Digital Library (Canada)

    6 juin 2016 ... Smart Cities for Sustainable Development. Elsa Estevez, Nuno Vasco Lopes et Tomasz Janowski. On prévoit que de 2014 à 2050, la population urbaine mondiale devrait croître de 63 pour cent, comparativement à une croissance de la population mondiale globale de 32 pour cent pendant la même ...

  20. Publications | Page 118 | CRDI - Centre de recherches pour le ...

    International Development Research Centre (IDRC) Digital Library (Canada)

    La culture du pavot à opium : quelle politique pour l'Afghanistan ? La culture illicite du pavot à opium contribue à la subsistance de millions de paysans afghans, mais il se trouve qu'elle constitue également une source de revenus importants pour les bandes criminalisées.

  1. Note - Des macrophytes pour épurer les eaux ?

    Directory of Open Access Journals (Sweden)

    BOUTIN, Catherine

    2014-12-01

    Full Text Available Utiliser des macrophytes pour mieux satisfaire les besoins humains est une part importante des recherches qui les concernent. Pour l’épuration des eaux usées et les aménagements associés, qu’en est-il ?

  2. A statistical treatment of bioassay pour fractions

    Science.gov (United States)

    Barengoltz, Jack; Hughes, David

    A bioassay is a method for estimating the number of bacterial spores on a spacecraft surface for the purpose of demonstrating compliance with planetary protection (PP) requirements (Ref. 1). The details of the process may be seen in the appropriate PP document (e.g., for NASA, Ref. 2). In general, the surface is mechanically sampled with a damp sterile swab or wipe. The completion of the process is colony formation in a growth medium in a plate (Petri dish); the colonies are counted. Consider a set of samples from randomly selected, known areas of one spacecraft surface, for simplicity. One may calculate the mean and standard deviation of the bioburden density, which is the ratio of counts to area sampled. The standard deviation represents an estimate of the variation from place to place of the true bioburden density commingled with the precision of the individual sample counts. The accuracy of individual sample results depends on the equipment used, the collection method, and the culturing method. One aspect that greatly influences the result is the pour fraction, which is the quantity of fluid added to the plates divided by the total fluid used in extracting spores from the sampling equipment. In an analysis of a single sample’s counts due to the pour fraction, one seeks to answer the question: What is the probability that if a certain number of spores are counted with a known pour fraction, that there are an additional number of spores in the part of the rinse not poured. This is given for specific values by the binomial distribution density, where detection (of culturable spores) is success and the probability of success is the pour fraction. A special summation over the binomial distribution, equivalent to adding for all possible values of the true total number of spores, is performed. This distribution when normalized will almost yield the desired quantity. It is the probability that the additional number of spores does not exceed a certain value. Of course

  3. Randomized, phase III study of gemcitabine or erlotinib maintenance therapy versus observation, with predefined second-line treatment, after cisplatin-gemcitabine induction chemotherapy in advanced non-small-cell lung cancer.

    Science.gov (United States)

    Pérol, Maurice; Chouaid, Christos; Pérol, David; Barlési, Fabrice; Gervais, Radj; Westeel, Virginie; Crequit, Jacky; Léna, Hervé; Vergnenègre, Alain; Zalcman, Gérard; Monnet, Isabelle; Le Caer, Hervé; Fournel, Pierre; Falchero, Lionel; Poudenx, Michel; Vaylet, Fabien; Ségura-Ferlay, Céline; Devouassoux-Shisheboran, Mojgan; Taron, Miquel; Milleron, Bernard

    2012-10-01

    This phase III study investigated whether continuation maintenance with gemcitabine or switch maintenance with erlotinib improves clinical outcome compared with observation in patients with advanced non-small-cell lung cancer (NSCLC) whose disease was controlled after cisplatin-gemcitabine induction chemotherapy. Four hundred sixty-four patients with stage IIIB/IV NSCLC without tumor progression after four cycles of cisplatin-gemcitabine were randomly assigned to observation or to gemcitabine (1,250 mg/m(2) days 1 and 8 of a 3-week cycle) or daily erlotinib (150 mg/day) study arms. On disease progression, patients in all three arms received pemetrexed (500 mg/m(2) once every 21 days) as predefined second-line therapy. The primary end point was progression-free survival (PFS). PFS was significantly prolonged by gemcitabine (median, 3.8 v 1.9 months; hazard ratio [HR], 0.56; 95% CI, 0.44 to 0.72; log-rank P benefit was consistent across all clinical subgroups. Both maintenance strategies resulted in a nonsignificant improvement in overall survival (OS); patients who received second-line pemetrexed or with a performance status of 0 appeared to derive greater benefit. Exploratory analysis showed that magnitude of response to induction chemotherapy may affect the OS benefit as a result of gemcitabine maintenance. Maintenance gemcitabine and erlotinib were well tolerated with no unexpected adverse events. Gemcitabine continuation maintenance or erlotinib switch maintenance significantly reduces disease progression in patients with advanced NSCLC treated with cisplatin-gemcitabine as first-line chemotherapy. Response to induction chemotherapy may affect OS only for continuation maintenance.

  4. Malignant thrombosis of the superior vena cava caused by non-small-cell lung cancer treated with radiation and erlotinib: a case with complete and prolonged response over 3 years

    Directory of Open Access Journals (Sweden)

    Wang JY

    2013-07-01

    Full Text Available Jianyang Wang,1 Jun Liang,1 Wenqing Wang,1 Han Ouyang,2 Luhua Wang11Department of Radiation Oncology, Cancer Hospital and Institute, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 2Department of Diagnostic Radiology, Cancer Hospital and Institute, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People's Republic of ChinaAbstract: Most cases of superior vena cava (SVC syndrome resulting from neoplasm, especially from lung cancer, remain a serious challenge to treat. Here, for the first time as far as we are aware, we report the case of a non-small-cell lung cancer patient with a massive SVC malignant thrombosis who was treated with thoracic irradiation and erlotinib. The treatment regimen consisted of erlotinib 150 mg/day and a total dose of 66 Gy/33 fractions delivered to the tumor, malignant thrombosis, and metastasis mediastinal lymph nodes. The malignant thrombosis responded dramatically and the combined regimen was well tolerated. After discharge, the erlotinib was prescribed as maintenance therapy. The patient was followed closely for the next 3 years. During this time, positron emission tomography/computed tomography scans and serum tumor marker screens were undertaken. By 6 months, the primary tumor showed complete response and by 9 months, the SVC thrombosis had disappeared. No sign of relapse has been found to date.Keywords: superior vena cava syndrome, radiotherapy, thoracic irradiation, neoplasm

  5. Pertuzumab and Erlotinib in Patients With Relapsed Non-Small Cell Lung Cancer: A Phase II Study Using 18F-Fluorodeoxyglucose Positron Emission Tomography/Computed Tomography Imaging

    Science.gov (United States)

    Mileshkin, Linda; Townley, Peter; Gitlitz, Barbara; Eaton, Keith; Mitchell, Paul; Hicks, Rodney; Wood, Katie; Amler, Lucas; Fine, Bernard M.; Loecke, David; Pirzkall, Andrea

    2014-01-01

    Background. Combination blockade of human epidermal growth factor receptor (HER) family signaling may confer enhanced antitumor activity than single-agent blockade. We performed a single-arm study of pertuzumab, a monoclonal antibody that inhibits HER2 dimerization, and erlotinib in relapsed non-small cell lung cancer (NSCLC). Methods. Patients received pertuzumab (840-mg loading dose and 420-mg maintenance intravenously every 3 weeks) and erlotinib (150-mg or 100-mg dose orally, daily). The primary endpoint was response rate (RR) by 18F-fluorodeoxyglucose positron emission tomography (FDG-PET) at day 56 in all patients and those with EGFR wild-type tumors. Results. Of 41 patients, 28 (68.3%) experienced treatment-related grade ≥3 adverse events, including pneumatosis intestinalis (3 patients), resulting in early cessation of enrollment. Tissue samples from 32 patients showed mutated EGFR status in 9 of 41 (22%) and wild-type EGFR in 23 of 41 (56%). The FDG-PET RR for patients with assessments at day 56 was 19.5% in all patients (n = 41) and 8.7% in patients with wild-type EGFR NSCLC (n = 23). Investigator-assessed computed tomography RR at day 56 was 12.2%. Conclusion. FDG-PET suggests that pertuzumab plus erlotinib is an active combination, but combination therapy was poorly tolerated, which limits its clinical applicability. More research is warranted to identify drug combinations that disrupt HER receptor signaling but that exhibit improved tolerability profiles. PMID:24457379

  6. De meilleurs emplois pour l'Asie | CRDI - Centre de recherches pour ...

    International Development Research Centre (IDRC) Digital Library (Canada)

    2 mars 2018 ... D'est en ouest, les économies de l'Asie se transforment rapidement, créant des emplois pour une population croissante de jeunes travailleurs. Cependant, qu'en est-il des conditions de travail ? Une recherche financée par le CRDI recueille des données probantes qui démontrent que de meilleures ...

  7. The concrete technology of post pouring zone of raft foundation of Hongyun Building B tower

    Science.gov (United States)

    Yin, Suhua; Yu, Liu; Wu, Yanli; Zhao, Ying

    2017-08-01

    The foundation of Hongyun building B tower is made of raft board foundation which is 3300mm in the thickness concreted pouring amount of large and the late poured band in the pouring settlement formed. The temperature of the pouring settlement was controlled in order to prevent the crack of the construction of the late poured band. The steel of post pouring band was designed and monitorred. The quality of post pouring band quality is guaranteed in the raft concrete foundation of Hongyun Building B tower.

  8. A lunguistica pour ses quarante ans

    Directory of Open Access Journals (Sweden)

    Ludvik Horvat Le Doyen

    2000-12-01

    Full Text Available En tant que doyen de la Faculté des Lettres de l'Universite de Ljubljana, j'ai l'honneur d'introduire le volume qui celebre les quarante ans de publication de cette revue linguistique. La parution de la revue conçua à l' origine comme supplàment pour la linguistique non slave de la revue Slavistična revija (dont la renommée était déjà affirmée, eut lieu en 1958. Ses inspirateurs, ses fondateurs et ses premiers directeurs, auxquels nous gardons une profonde reconnaissance, furent l'italianiste Stanko Škerlj et le latiniste Milan Grošelj, professeurs de notre Faculté. Des sa quatrieme année ce modeste supplement devint revue autonome, telle que nous la connaissons aujourd'hui.

  9. APPARATUS FOR MELTING AND POURING METAL

    Science.gov (United States)

    Harris, F.A.

    1958-02-25

    This patent relates to a crucible for melting and pouring a metal under controlled atmospheric conditions. The crucible has a frangible plug in the bottom and a retaining device to prevent the entrance of the broken portions of the plug into the mold without interfering with the flow of the melt. After the charge has been melted, a knockout rod is lowered through the charge and forced against the frangible plug sufficiently to break off the closure disk along a previously scored line. The disk drops onto a retaining grid large enough to permit the flow of metal around the disk and into the mold below. Thts arrangement elimnates the entry of broken portions of the plug into the mold, thereby elimnating a common cause of imperfect castings.

  10. Evaluation of the VeriStrat® serum protein test in patients with advanced squamous cell carcinoma of the lung treated with second-line afatinib or erlotinib in the phase III LUX-Lung 8 study.

    Science.gov (United States)

    Gadgeel, Shirish; Goss, Glenwood; Soria, Jean-Charles; Felip, Enriqueta; Georgoulias, Vassilis; Lu, Shun; Cobo, Manuel; Syrigos, Konstantinos; Lee, Ki Hyeong; Göker, Erdem; Guclu, Salih Z; Isla, Dolores; Morabito, Alessandro; Dupuis, Nicholas; Bühnemann, Claudia; Krämer, Nicole; Solca, Flavio; Ehrnrooth, Eva; Ardizzoni, Andrea

    2017-07-01

    Identification of biomarkers associated with clinical benefit may be crucial in establishing optimal treatment choice for patients with squamous cell carcinoma (SCC) of the lung after first-line chemotherapy. In this study, the ability of the VeriStrat serum protein test to predict differential clinical benefit with afatinib versus erlotinib, and the association of VeriStrat status with clinical outcomes irrespective of EGFR-TKI used, was assessed in a retrospective analysis of the phase III LUX-Lung 8 trial. Pretreatment plasma samples were analyzed using matrix-assisted laser desorption ionization time-of-flight mass spectrometry. Spectra were evaluated to assign a VeriStrat 'Good' (VS-G) or VeriStrat 'Poor' (VS-P) classification. Overall survival (OS), progression-free survival, and other endpoints were assessed with respect to pretreatment VeriStrat status; OS was the primary efficacy variable. Outcomes with other efficacy endpoints were similar. Of 795 patients randomized in LUX-Lung 8, 675 were classified (VS-G: 412; VS-P: 263). In the VS-G group, OS was significantly longer with afatinib versus erlotinib (HR 0.79 [95% CI: 0.63-0.98]). In the VS-P group, there was no significant difference in OS between afatinib and erlotinib (HR 0.90 [0.70-1.16]). However, there was no interaction between VeriStrat classification and treatment group for OS (p interaction =0.5303). OS was significantly longer in VS-G versus VS-P patients, both in the overall VeriStrat-classified population (HR 0.41 [0.35-0.49]) and afatinib-treated patients (HR 0.40 [0.31-0.51]). Multivariate analysis showed that VeriStrat was an independent predictor of OS in afatinib-treated patients, regardless of ECOG PS or best response to first-line chemotherapy. VS-G classification is strongly associated with favorable survival outcomes with either afatinib or erlotinib compared with VS-P classification. In VS-G patients, survival outcomes with afatinib are superior to those with erlotinib. Veri

  11. Adding Erlotinib to Chemoradiation Improves Overall Survival but Not Progression-Free Survival in Stage III Non-Small Cell Lung Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Komaki, Ritsuko, E-mail: rkomaki@mdanderson.org [Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Allen, Pamela K.; Wei, Xiong [Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Blumenschein, George R. [Department of Thoracic Head and Neck Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Tang, Ximing [Department of Translational Molecular Pathology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Lee, J. Jack [Department of Biostatatistics, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Welsh, James W. [Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Wistuba, Ignacio I. [Department of Translational Molecular Pathology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Liu, Diane D. [Department of Biostatatistics, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Hong, Waun Ki [Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States)

    2015-06-01

    Purpose: To test, in a single-arm, prospective, phase 2 trial, whether adding the epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor erlotinib to concurrent chemoradiotherapy for previously untreated, locally advanced, inoperable non-small cell lung cancer would improve survival and disease control without increasing toxicity. Methods and Materials: Forty-eight patients with previously untreated non-small cell lung cancer received intensity modulated radiation therapy (63 Gy/35 fractions) on Monday through Friday, with chemotherapy (paclitaxel 45 mg/m², carboplatin area under the curve [AUC] = 2) on Mondays, for 7 weeks. All patients also received the EGFR tyrosine kinase inhibitor erlotinib (150 mg orally 1/d) on Tuesday-Sunday for 7 weeks, followed by consolidation paclitaxel–carboplatin. The primary endpoint was time to progression; secondary endpoints were overall survival (OS), toxicity, response, and disease control and whether any endpoint differed by EGFR mutation status. Results: Of 46 patients evaluable for response, 40 were former or never-smokers, and 41 were evaluable for EGFR mutations (37 wild-type [WT] and 4 mutated [all adenocarcinoma]). Median time to progression was 14.0 months and did not differ by EGFR status. Toxicity was acceptable (no grade 5, 1 grade 4, 11 grade 3). Twelve patients (26%) had complete responses (10 WT, 2 mutated), 27 (59%) partial (21 WT, 2 mutated, 4 unknown), and 7 (15%) none (6 WT, 2 mutated, 1 unknown) (P=.610). At 37.0 months' follow-up (range, 3.6-76.5 months) for all patients, median OS time was 36.5 months, and 1-, 2-, and 5-year OS rates were 82.6%, 67.4%, and 35.9%, respectively; none differed by mutation status. Twelve patients had no progression, and 34 had local and/or distant failure. Eleven of 27 distant failures were in the brain (7 WT, 3 mutated, 1 unknown). Conclusions: Toxicity and OS were promising, but time to progression did not meet expectations. The prevalence of

  12. Modelisation des effets physico-techniques pour la conception des ...

    African Journals Online (AJOL)

    automatisation dans les installations industrielles a besoin d'une régulation automatique des commandes des processus technologiques pour lesquelles certaines contraintes sont à relever compte tenu des exigences des innovations scientifiques de ...

  13. Nouveaux centres de cyberpolitique pour les pays du Sud | IDRC ...

    International Development Research Centre (IDRC) Digital Library (Canada)

    13 avr. 2018 ... L'appel ouvert avait pour but de cibler les organismes indépendants voués à la recherche sur les politiques qui s'appuient sur la recherche pour éclairer et influencer les politiques nationales dans les domaines des droits numériques, de la cybersécurité et des politiques d'innovation. Parmi les 59 ...

  14. Centre de recherches pour le développement international ...

    International Development Research Centre (IDRC) Digital Library (Canada)

    André Lavoie

    Definitions. 5. Rôles et ... a) Le Centre de recherches pour le développement international (CRDI) est une société d'État canadienne à .... conduite éthique dans le cadre de ces activités afin que la confiance du public dans .... a) Les gouverneurs en déplacement pour le compte du CRDI ont droit à une indemnité de repas et ...

  15. Ethiopia : tous les projets | CRDI - Centre de recherches pour le ...

    International Development Research Centre (IDRC) Digital Library (Canada)

    Le but de ce projet consiste à améliorer la compréhension des complexités du mariage d'enfants et de la parentalité pour éclairer les politiques et les programmes. Sujet: Gender. Région: Ethiopia, Peru, Zambia. Programme: Gouvernance et justice. Financement total : CA$ 1,120,200.00. Alliance statistique pour les faits ...

  16. Images du Mage, images pour le Mage

    Directory of Open Access Journals (Sweden)

    Daniel GREGORIO

    2007-01-01

    Full Text Available Les œuvres d’Alphonse X proposent diverses représentations du mage, qui en font, tour à tour, l’ennemi ou l’allié de la religion chrétienne. Il est vrai que parfois, comme le montre l’histoire de Simon le magicien, la pratique de la magie implique un commerce direct et néfaste avec les forces infernales. Néanmoins, les personnages de Merlin et des Rois Mages, tels qu’ils sont présentés par Alphonse X, démontrent que magie et religion peuvent cohabiter, à condition toutefois que le mage croit en la virginité de Marie et en l’Incarnation et que sa pratique magique soit bénéfique pour la communauté. Ce bénéfice requiert parfois la reconstruction de l’univers quotidien ; pour ce faire, le magicien doit savoir quand et comment utiliser des objets et des pentacles, qui lui permettront de soumettre les forces surnaturelles. Il doit donc posséder une connaissance approfondie du monde naturel et des esprits qui, conjuguée à sa foi religieuse, l’empêchera de tomber dans la démonolâtrie.Las obras alfonsíes proponen diversas aproximaciones al personaje del mago, generalmente considerado como un ser antagónico del hombre religioso. Es cierto que en algunas ocasiones, como ocurre con Simón el mago, la práctica de las artes mágicas significa un trato directo y nefasto con las fuerzas infernales. Sin embargo, personajes como Merlín o los Reyes Magos, tal y como los describe Alfonso X, subrayan una posible cohabitación entre magia y religión sin que la práctica de la una signifique la exclusión de la otra. Sólo hay que cumplir con dos condiciones : creer en la virginidad de María y que Dios se hizo hombre, y proporcionar a la comunidad un beneficio claro. Este beneficio requiere en ocasiones remodelar lo cotidiano, utilizando objetos y pentáculos, en circunstancias extremadamente determinadas, lo que implica un conocimiento exhaustivo tanto del mundo natural como del simbólico y de los espíritus. Es este

  17. Pour une ingénierie des Environnements Informatiques pour l'Apprentissage Humain

    OpenAIRE

    Tchounikine , Pierre

    2002-01-01

    Nous proposons dans cet article une réflexion sur la notion d'ingénierie des EIAH (Environnements Informatiques pour l'Apprentissage Humain). Nous posons tout d'abord une définition de l'ingénierie des EIAH : travaux visant à définir des éléments de méthodes et de techniques reproductibles et/ou réutilisables facilitant la mise en place (conception – réalisation – expérimentation – évaluation - diffusion) d'environnements de formation ou d'apprentissage (dans leur articulation avec les dispos...

  18. Comment agir pour raviver l'espoir ? Pour un traitement efficace du ...

    International Development Research Centre (IDRC) Digital Library (Canada)

    28 févr. 2011 ... Dix pour cent de la population mondiale vit dans cette région qui affiche près de 70 % des cas d'infection par le VIH dans le monde et 90 % des décès causés par le sida. En 2005, on y a relevé environ 2,7 millions de nouveaux cas, ce qui porterait à 24,5 millions le nombre de personnes vivant avec le ...

  19. ALGORITHME POUR LE CALCUL DES COURBURES GENERALISEES

    Directory of Open Access Journals (Sweden)

    K MEZAGHCHA

    2004-06-01

    Full Text Available On sait qu’une courbe algébrique standard  d'équation f(x, y =0 admet un nombre fini de branches (nombre inférieur à l'ordre de f , dont les paramètrages peuvent être obtenus en particulier à partir de la décomposition de Goze itérée. On aimerait calculer  leur courbure généralisée sans les déterminer explicitement, la notion de courbure généralisée ayant fait l’objet d’un travail, publié dans les comptes rendus de l’Université de Cagliari (Italie [12]. Dans cet article, on se propose d'établir à cet effet un algorithme qui donnera à partir seulement des coefficients de f, la liste exhaustive des courbures généralisées de toutes les branches réelles. L’article se termine par la donnée d’un exemple pour montrer l’efficacité de l’algorithme proposé.

  20. Un ticket pour la liberté

    Directory of Open Access Journals (Sweden)

    Nabil Mouline

    2014-07-01

    Full Text Available Pour diverses raisons, l’industrie cinématographique égyptienne a connu des changements profonds au début des années 2000. L’une des conséquences les plus palpables a été la production de manière volontaire ou involontaire de films contestataires dans la mesure où ils essaient de remettre en cause le discours dominant et de lever le tabou sur plusieurs questions sociopolitiques. Cela a fait du produit filmique non seulement un document d’archive qui reflète l’état de la société mais également un outil efficace de soft influence et de mobilisation qui a participé à la création d’une communauté imaginée dont une partie est passée à l’action le 25 janvier 2011. C’est l’ambition de cet article que de lever le voile sur ce double rôle du cinéma entre 2001 et 2010 en s’appuyant sur un large échantillon de films à grand succès.

  1. Avaliação económica do erlotinib, docetaxel, pemetrexedo e tratamento de suporte no tratamento de segunda ou terceira linhas de doentes com cancro do pulmão de não pequenas células An economic analysis of erlotinib, docetaxel, pemetrexed and best supportive care as second or third line treatment of non-small cell lung cancer

    Directory of Open Access Journals (Sweden)

    A Araújo

    2008-12-01

    Full Text Available Objectivo: Avaliar o custo-efectividade de erlotinib na segunda ou terceira linha do tratamento do cancro do pulmão de não pequenas células (CPNPC avançado ou metastizado versus docetaxel, pemetrexedo ou tratamento de suporte. Material e métodos: Análises de minimização de custos e custo-utilidade. Horizonte temporal: dois anos. Perspectiva do Sistema Nacional de Saúde (SNS português. Sobrevivência e tempo até progressão obtidos a partir de três ensaios clínicos. Análise-base inclui doentes com CPNPC avançado ou metastizado em segunda ou terceira linhas. Anos de vida ajustados pela qualidade (ou QALY obtidos a partir de estudo no Reino Unido. Consumo de recursos estimado por painel de peritos portugueses. Incluíram-se apenas custos directos, obtidos a partir de fontes oficiais (preços actualizados para 2008. Taxa de actualização anual: 5%. Análises de sensibilidade: diferentes subpopulações, horizonte temporal a três anos e análise probabilística. Resultados: O custo total/doente foi menor com erlotinib (26 478€ versus docetaxel (29 262€ ou pemetrexedo (32 762€ e superior versus tratamento de suporte (16 112€. Obtiveram-se QALY/doente mais elevados com erlotinib (0,250 versus docetaxel (0,225, pemetrexedo (0,241 ou tratamento de suporte (0,186. Assim, o erlotinib mostrou-se “dominante” em segunda ou terceira linhas versus docetaxel e pemetrexedo. A análise de sensibilidade comprova a robustez dos resultados. Conclusões: A substituição de docetaxel ou pemetrexedo por erlotinib poderia contribuir para uma redução anual dos gastos do SNS que se estima (taxas substituição: 5%-65% com uma variação entre 135 046€-1 755 602€ e entre 291 801€ -3 793 409€, respectivamente, e com ganho em termos de QALY.Aim: Evaluate costs and benefits of erlotinib as 2nd or 3rd line treatment of advanced or metastatic nonsmall cell lung cancer (NSCLC versus docetaxel, pemetrexed and best supportive care. Materials

  2. Erlotinib no tratamento de segunda linha do cancro do pulmão de não pequenas células. Caso clínico

    Directory of Open Access Journals (Sweden)

    Mariana Sousa

    2008-10-01

    Full Text Available Resumo: Homem, de 58 anos, caucasiano, trabalhador da construção civil, sem hábitos tabágicos, com antecedentes pessoais de síndroma depressiva (medicado com quetiapina, litíase vesicular, quistos renais, cirurgia por pólipos intestinais benignos e antecedentes familiares de neoplasias – pulmonar da tia materna e intestinal da mãe. Iniciou quadro de toracalgia e vómitos, pelo que fez radiografia do tórax, que evidenciou opacidade basal direita. Realizou estudo etiológico, sendo submetido a toracotomia em Abril de 2006, que demonstrou presença de “granulações finas, disseminadas por todo o campo pulmonar” e cujo diagnóstico histológico foi carcinoma adenoescamoso de pulmão (16/05/2006. Iniciou tratamento citostático com vinorelbina-carboplatino em 02/06/2006, com toxicidade hematológica grau III –IV, pelo que, embora com doença estável, iniciou segunda linha terapêutica com erlotinib, em 11/06/2007, que fez sem desenvolver efeitos secundários significativos. Em Outubro de 2007, apresentou quadro de nevralgia do trigémio, cujo estudo subsequente revelou meningioma esfenopetroclival direito. Apresentou metastização cerebral, suspendendo erlotinib em 09/06/2008. Foi submetido a neuroradiocirurgia e actualmente está sob trata-mento sintomático de suporte.Rev Port Pneumol 2008; XIV (Supl 3: S79-S82 Abstract: Male, of 58 years, caucasian, construction worker, non smoker, with depressive syndrome, biliary lithiasis, renal cysts, surgery for benign intestinal polyps and relevant familiar history – aunt with lung cancer and mother with colon cancer. He initiated thorax pain and vomitting and made a chest x-ray, showing a right basal lung mass. During the etiologic study, he was submitted to thoracotomy with biopsy, in April 2006 – “fine granulations, spread for all the pulmonary field”, allowing the diagnosis – adenosquamous

  3. Investigation of waste glass pouring behavior over a knife edge

    International Nuclear Information System (INIS)

    Ebadian, M.A.

    1998-01-01

    The development of vitrification technology for converting radioactive waste into a glass solid began in the early 1960s. Some problems encountered in the vitrification process are still waiting for a solution. One of them is wicking. During pouring, the glass stream flows down the wall of the pour spout until it reaches an angled cut in the wall. At this point, the stream is supposed to break cleanly away from the wall of the pour spout and fall freely into the canister. However, the glass stream is often pulled toward the wall and does not always fall into the canister, a phenomenon known as wicking. Phase 1 involves the assembly, construction, and testing of a melter capable of supplying molten glass at operational flow rates over a break-off point knife edge. Phase 2 will evaluate the effects of glass and pour spout temperatures as well as glass flow rates on the glass flow behavior over the knife edge. Phase 3 will identify the effects on wicking resulting from varying the knife edge diameter and height as well as changing the back-cut angle of the knife edge. The following tasks were completed in FY97: Design the experimental system for glass melting and pouring; Acquire and assemble the melter system; and Perform initial research work

  4. Paired Phase II Studies of Erlotinib/Bevacizumab for Advanced Bronchioloalveolar Carcinoma or Never Smokers With Advanced Non-Small-cell Lung Cancer: SWOG S0635 and S0636 Trials.

    Science.gov (United States)

    West, Howard L; Moon, James; Wozniak, Antoinette J; Mack, Philip; Hirsch, Fred R; Bury, Martin J; Kwong, Myron; Nguyen, Dorothy D; Moore, Dennis F; Miao, Jieling; Redman, Mary; Kelly, Karen; Gandara, David R

    2018-01-01

    Before mutation testing of the epidermal growth factor receptor (EGFR) gene was recognized as highly associated with the activity of EGFR tyrosine kinase inhibitors (TKIs), clinically defined patient populations with bronchioloalveolar carcinoma (BAC) and never smokers were identified as likely to benefit from EGFR TKIs. From preclinical and clinical data suggesting potentially improved efficacy with a combination of an EGFR TKI and the antiangiogenic agent bevacizumab, the Southwestern Oncology Group (SWOG) initiated paired phase II trials to evaluate the combination of erlotinib/bevacizumab in patients with advanced BAC (SWOG S0635) or never smokers with advanced lung adenocarcinoma (SWOG S0636). Eligible patients with BAC or adenocarcinoma with BAC features (SWOG S0635) or never smokers with advanced lung adenocarcinoma (SWOG S0636) received erlotinib 150 mg/day with bevacizumab 15 mg/kg until progression or prohibitive toxicity. Never smokers with BAC were preferentially enrolled to SWOG S0636. The primary endpoint for both trials was overall survival. A total of 84 patients were enrolled in the SWOG S0635 trial and 85 in the SWOG S0636 trial. The objective response rate was 22% (3% complete response) in the SWOG S0635 trial and 50% (38% confirmed; 3% complete response) in the SWOG S0636 trial. The median progression-free survival was 5 and 7.4 months in the S0635 and S0636 trials, respectively. The median overall survival was 21 and 29.8 months, respectively. Toxicity consisted mainly of rash and diarrhea in both trials. Although the field has moved toward molecular, rather than clinical, selection of patients as optimal candidates for EGFR TKI therapy, these results support the hypothesis that a subset of patients in whom erlotinib is particularly active could receive an incremental benefit from the addition of bevacizumab. Copyright © 2017 Elsevier Inc. All rights reserved.

  5. Ablation laser pour la microélectronique plastique

    Science.gov (United States)

    Alloncle, A.-P.; Thomas, B.; Grojo, D.; Delaporte, Ph.; Sentis, M.; Sanaur, S.; Barret, M.; Collot, Ph.

    2006-12-01

    La microélectronique plastique connaît un développement sans précédent dans le domaine de la recherche. Cette étude s'intéresse à l'utilisation des lasers impulsionnels pour la réalisation de composants organiques sur supports souples. Les deux aspects plus particulièrement étudiés sont d'une part la gravure de polymère pour réaliser un canal entre la source et le drain, et d'autre part le développement d'un procédéde dépôt appelé LIFT pour Laser Induced Forward Transfer. Ce dernier pourrait notamment permettre dedéposer des composés organiques non solubles.

  6. Compliance with PET acquisition protocols for therapeutic monitoring of erlotinib therapy in an international trial for patients with non-small cell lung cancer

    International Nuclear Information System (INIS)

    Binns, David S.; Callahan, Jason; Mileshkin, Linda; Pirzkall, Andrea; Yu, Wei; Fine, Bernard M.; Conti, Peter; Scott, Andrew M.; Macfarlane, David; Hicks, Rodney J.

    2011-01-01

    The Response Evaluation Criteria in Solid Tumors (RECIST) are widely used but have recognized limitations. Molecular imaging assessments, including changes in 18 F-deoxyglucose (FDG) or 18 F-deoxythymidine (FLT) uptake by positron emission tomography (PET), may provide earlier, more robust evaluation of treatment efficacy. A prospective trial evaluated on-treatment changes in FDG and FLT PET imaging among patients with relapsed or recurrent non-small cell lung cancer treated with erlotinib to assess the relationship between PET-evaluated response and clinical outcomes. We describe an audit of compliance with the study imaging charter, to establish the feasibility of achieving methodological consistency in a multicentre setting. Patients underwent PET scans at baseline and approximately day 14 and day 56 of treatment (n = 73, 66 and 51 studies, and n = 73, 63 and 50 studies for FDG PET and FLT PET, respectively). Blood glucose levels were within the target range for all FDG PET scans. Charter-specified uptake times were achieved in 86% (63/73) and 89% (65/73) of baseline FDG and FLT scans, respectively. On-treatment scans were less consistent: 72% (84/117) and 68% (77/113), respectively, achieved the target of ±5 min of baseline uptake time. However, 96% (112/117) and 94% (106/113) of FDG and FLT PET studies, respectively, were within ±15 min. Bland-Altman analysis of intra-individual hepatic average standardized uptake value (SUV ave ), to assess reproducibility, showed only a small difference in physiological uptake (-0.006 ± 0.224 in 118 follow-up FDG scans and 0.09 ± 0.81 in 111 follow-up FLT scans). It is possible to achieve high reproducibility of scan acquisition methodology, provided that strict imaging compliance guidelines are mandated in the study protocol. (orig.)

  7. Compliance with PET acquisition protocols for therapeutic monitoring of erlotinib therapy in an international trial for patients with non-small cell lung cancer

    Energy Technology Data Exchange (ETDEWEB)

    Binns, David S.; Callahan, Jason; Mileshkin, Linda [The Peter MacCallum Cancer Centre, Melbourne (Australia); Pirzkall, Andrea; Yu, Wei; Fine, Bernard M. [Genentech, Inc., South San Francisco, CA (United States); Conti, Peter [University of Southern California Kenneth Norris Medical Center, Los Angeles, CA (United States); Scott, Andrew M. [The University of Melbourne and The Austin Hospital, Centre for PET, and Ludwig Institute for Cancer Research, Victoria (Australia); Macfarlane, David [Queensland PET Service, Royal Brisbane and Women' s Hospital, Brisbane (Australia); Hicks, Rodney J. [The University of Melbourne and The Peter MacCallum Cancer Centre, Departments of Medicine and Radiology, East Melbourne, VIC (Australia); The Peter MacCallum Cancer Centre, Melbourne (Australia)

    2011-04-15

    The Response Evaluation Criteria in Solid Tumors (RECIST) are widely used but have recognized limitations. Molecular imaging assessments, including changes in {sup 18}F-deoxyglucose (FDG) or {sup 18}F-deoxythymidine (FLT) uptake by positron emission tomography (PET), may provide earlier, more robust evaluation of treatment efficacy. A prospective trial evaluated on-treatment changes in FDG and FLT PET imaging among patients with relapsed or recurrent non-small cell lung cancer treated with erlotinib to assess the relationship between PET-evaluated response and clinical outcomes. We describe an audit of compliance with the study imaging charter, to establish the feasibility of achieving methodological consistency in a multicentre setting. Patients underwent PET scans at baseline and approximately day 14 and day 56 of treatment (n = 73, 66 and 51 studies, and n = 73, 63 and 50 studies for FDG PET and FLT PET, respectively). Blood glucose levels were within the target range for all FDG PET scans. Charter-specified uptake times were achieved in 86% (63/73) and 89% (65/73) of baseline FDG and FLT scans, respectively. On-treatment scans were less consistent: 72% (84/117) and 68% (77/113), respectively, achieved the target of {+-}5 min of baseline uptake time. However, 96% (112/117) and 94% (106/113) of FDG and FLT PET studies, respectively, were within {+-}15 min. Bland-Altman analysis of intra-individual hepatic average standardized uptake value (SUV{sub ave}), to assess reproducibility, showed only a small difference in physiological uptake (-0.006 {+-} 0.224 in 118 follow-up FDG scans and 0.09 {+-} 0.81 in 111 follow-up FLT scans). It is possible to achieve high reproducibility of scan acquisition methodology, provided that strict imaging compliance guidelines are mandated in the study protocol. (orig.)

  8. Skin rash in patients treated with neoadjuvant erlotinib (Tarceva in resectable non-small cell lung cancer: Predictor for tumor response and survival?

    Directory of Open Access Journals (Sweden)

    Van Gool MH

    2017-08-01

    Full Text Available Background: Skin rash during treatment with epidermal growth factor receptor (EGFR-tyrosine kinase inhibitors (TKI has been reported to be predictive for response and survival in patients with advanced non-small cell lung cancer (NSCLC. The aim of this analysis was to evaluate whether skin rash during treatment (as a biomarker in a preoperative setting was related to response and survival. Methods: This study was designed as an open-label phase II trial (also known as M06NEL. Patients received preoperative erlotinib (Tarceva 150 mg once daily for 3 weeks. Skin toxicity during treatment was analysed in relation to metabolic and histopathological response, overall survival (OS and progression-free survival (PFS. Results: In total 59 patients (25 male, 34 female were eligible for analysis. In 39 patients (66% skin toxicity occurred. According to National Cancer Institute Common Toxicity Criteria (NCICTC, Grade 1 toxicity was seen in 15 patients (25%, Grade 2 in 19 patients (32% and Grade 3 in five patients (8%. None of the patients showed skin toxicity Grade 4 and 5. The median follow up was 74 months. Thirty-six patients (61% were alive at time of analysis. Twenty-seven patients (46% showed disease progression during follow up. Hazard ratios (HR indicated lower risk of death (HR = 0.66, 95%CI: 0.29 - 1.50 and progression (HR = 0.64, 0.30 - 1.36, although in this small group results were not significant. Skin rash did not adequately predict response. Conclusions: In this neoadjuvant setting with limited treatment time in patients with early stage NSCLC, skin rash was not associated with response and survival and cannot be used as an early biomarker.

  9. Comparative studies on the human serum albumin binding of the clinically approved EGFR inhibitors gefitinib, erlotinib, afatinib, osimertinib and the investigational inhibitor KP2187.

    Science.gov (United States)

    Dömötör, Orsolya; Pelivan, Karla; Borics, Attila; Keppler, Bernhard K; Kowol, Christian R; Enyedy, Éva A

    2018-05-30

    Binding interactions between human serum albumin (HSA) and four approved epidermal growth factor receptor (EGFR) inhibitors gefitinib (GEF), erlotinib (ERL), afatinib (AFA), osimertinib (OSI), as well as the experimental drug KP2187, were investigated by means of spectrofluorometric and molecular modelling methods. Steady-state and time resolved spectrofluorometric techniques were carried out, including direct quenching of protein fluorescence and site marker displacement measurements. Proton dissociation processes and solvent dependent fluorescence properties were investigated as well. The EGFR inhibitors were predominantly presented in their single protonated form (HL + ) at physiological pH except ERL, which is charge-neutral. Significant solvent dependent fluorescence properties were found for GEF, ERL and KP2187, namely their emission spectra show strong dependence on the polarity and the hydrogen bonding ability of the solvents. The inhibitors proved to be bound at site I of HSA (in subdomain IIA) in a weak-to-moderate fashion (logK' 3.9-4.9) using spectrofluorometry. OSI (logK' 4.3) and KP2187 can additionally bind in site II (in subdomain IIIA), while GEF, ERL and AFA clearly show no interaction here. Docking methods qualitatively confirmed binding site preferences of compounds GEF and KP2187, and indicated that they probably bind to HSA in their neutral forms. Binding constants calculated on the basis of the various experimental data indicate a weak-to-moderate binding on HSA, only OSI exhibits somewhat higher affinity towards this protein. However, model calculations performed at physiological blood concentrations of HSA resulted in high (ca. 90%) bound fractions for the inhibitors, highlighting the importance of plasma protein binding. Copyright © 2018 Elsevier B.V. All rights reserved.

  10. Guide pour la conception des dispositifs de franchissement des barrages pour les poissons migrateurs

    Directory of Open Access Journals (Sweden)

    LARINIER M.

    1983-10-01

    Full Text Available L'auteur rappelle dans cette note les principes de base devant guider le projeteur lors de la conception des ouvrages de franchissement de barrages ou d'obstacles pour les poissons migrateurs. L'accent est mis sur l'importance de la situation et de l'attractivité de ces ouvrages. Les principes de fonctionnement et les critères de dimensionnement des différents types de passes (passes à bassins successifs, passes à ralentisseurs, écluses et ascenseurs sont évoqués. Dans la dernière partie sont recensés les éléments à prendre en compte lors de l'établissement d'un projet de passe.

  11. identification de caractéristiques agronomiques pour le diagnostic

    African Journals Online (AJOL)

    ACSS

    La régénération des vieux vergers de cacaoyers (Theobrama cacao L.) est une des stratégies mises en place en. Côte d'Ivoire pour assurer une production durable de cacao. Une étude a été conduite en vue d'élaborer un guide pour réaliser un diagnostic rapide et adéquat des vergers et prendre la bonne décision de ...

  12. Pouring rights contracts and childhood overweight: a critical theory perspective.

    Science.gov (United States)

    Opalinski, Andra

    2006-10-01

    To examine school environments, and in particular, pouring rights contracts and how they relate to childhood overweight from a critical theory perspective. Pouring rights contracts provide a profit to powerful mega-corporations at the expense of children's health. There is a need to move beyond a solely individual approach to addressing childhood overweight and involve a social ecology approach. This would involve a push for social change, including removal of soda machines from schools, and changing marketing practices targeted at children. Nurses are poised in community situations to actively effect social changes to improve health outcomes of our nation's most vulnerable people, but nurses must get involved.

  13. Publications | Page 57 | CRDI - Centre de recherches pour le ...

    International Development Research Centre (IDRC) Digital Library (Canada)

    Pour augmenter la production et l'offre de petits mils, les ménages ruraux doivent avoir accès à des technologies et à des... La gestion intégrée des pêches accroît la sécurité alimentaire en Amazonie bolivienne. En indiquant de nouveaux débouchés pour le poisson, en améliorant les connaissances en matière de nutrition ...

  14. Développement Odoo pour la gestion de pièces de rechange, pour un client de SOGESI.

    OpenAIRE

    BENFEDEL, Ahmed; KAZI AOUL, Abdessamad

    2016-01-01

    Ce stage de fin d’études a été une occasion pour nous pour une immersion dans le monde des ERP et de l’entreprise avec plus de responsabilités. Dans notre projet de fin d’études, le travail a été réalisé au sein de la société SOGESI. Dans ce cadre, nous avons travaillé sur un projet réel et un besoin bien spécifique d’une entreprise cliente de la société SOGESI. Pour ce faire, nous avons commencé par l’analyse des besoins, Par la suite, nous nous s...

  15. Randomized Phase III Trial of Erlotinib versus Docetaxel in Patients with Advanced Squamous Cell Non-Small Cell Lung Cancer Failing First-Line Platinum-Based Doublet Chemotherapy Stratified by VeriStrat Good versus VeriStrat Poor. The European Thoracic Oncology Platform (ETOP) EMPHASIS-lung Trial

    NARCIS (Netherlands)

    Peters, Solange; Stahel, Rolf A.; Dafni, Urania; Ponce Aix, Santiago; Massuti, Bartomeu; Gautschi, Oliver; Coate, Linda; Lopez Martin, Ana; van Heemst, Robbert; Berghmans, Thierry; Meldgaard, Peter; Cobo Dols, Manuel; Garde Noguera, Javier; Curioni-Fontecedro, Alessandra; Rauch, Daniel; Mark, Michael T.; Cuffe, Sinead; Biesma, Bonne; van Henten, Arjen M. J.; Juan Vidal, Oscar; Palmer Sanchez, Ramon; Villa Guzman, Jose Carlos; Collado Martin, Ricardo; Peralta, Sergio; Insa, Amelia; Summers, Yvonne; Lang, Istvan; Horgan, Anne; Ciardiello, Fortunato; de Hosson, Sander; Pieterman, Remge; Groen, Harry J. M.; van den Berg, Paul M.; Zielinski, Christoph C.; Kuruvilla, Yojena Chittazhathu Kurian; Gasca-Ruchti, Adriana; Kassapian, Marie; Novell, Silvia; Torri, Valter; Tsourti, Zoi; Gregorc, Vanesa; Smit, Egbert F.

    Introduction: Docetaxel and erlotinib are registered second line treatments for wild-type EGFR NSCLC. Previous studies suggested a predictive value of the VeriStrat test in second line therapy of NSCLC, classifying patients as either VeriStrat good or VeriStrat poor. EMPHASIS-lung aimed at exploring

  16. Publications | Page 40 | CRDI - Centre de recherches pour le ...

    International Development Research Centre (IDRC) Digital Library (Canada)

    Amérique du Nord et de l'Europe pour inclure maintenant un plus grand nombre d'établissements de recherche africains. Activité antérieure : Le CRDI au Congrès mondial sur la santé publique 2015. Le 14e Congrès mondial sur la santé publique ...

  17. Bourses de recherche pour la lutte antitabac en Afrique | IDRC ...

    International Development Research Centre (IDRC) Digital Library (Canada)

    ... charge de morbidité croissante liée aux maladies non transmissibles (MNT) dans les ... les compétences en recherche et les connaissances en Afrique pour garantir la ... Prevalence and predictors of cigarette smoking among adolescents of ...

  18. Initiative Think tank | CRDI - Centre de recherches pour le ...

    International Development Research Centre (IDRC) Digital Library (Canada)

    L'ITT est le fruit d'un partenariat regroupant cinq bailleurs de fonds. Lancée en 2008, l'ITT est administrée par le Centre de Recherches pour le Développement International (CRDI), un organisme canadien.

  19. Ce que nous faisons | CRDI - Centre de recherches pour le ...

    International Development Research Centre (IDRC) Digital Library (Canada)

    Le CRDI appuie des travaux de recherche dans les pays en voie de développement en vue de produire un changement réel et durable. Ce savoir peut servir d'outil pour résoudre des problèmes mondiaux urgents. Nous partageons ce savoir avec les autres en :

  20. Publications | Page 160 | CRDI - Centre de recherches pour le ...

    International Development Research Centre (IDRC) Digital Library (Canada)

    africain. Il y a deux ans, le Centre de recherches pour le développement ... African Youth on the Information Highway : Participation and Leadership in Community Development. Tout comme elle l'a fait dans le Nord industrialisé, la révolution de ...

  1. Publications | Page 162 | CRDI - Centre de recherches pour le ...

    International Development Research Centre (IDRC) Digital Library (Canada)

    africain. Il y a deux ans, le Centre de recherches pour le développement ... African Youth on the Information Highway : Participation and Leadership in Community Development. Tout comme elle l'a fait dans le Nord industrialisé, la révolution de ...

  2. nigeria : tous les projets | CRDI - Centre de recherches pour le ...

    International Development Research Centre (IDRC) Digital Library (Canada)

    ... des gouvernements étrangers ont eu des effets économiques positifs tout comme ... L'accès à Internet est devenu une priorité pour les pays en développement. ... les régions rurales mal desservies du Nigeria grâce à la recherche visant la ...

  3. Un programme de conservation pour l'ibis chauve (Geronticus ...

    African Journals Online (AJOL)

    dix couples au Maroc et trois couples récemment découverts en Syrie. De nombreuses actions ont été entrepris au Maroc pour la conservation de l'ibis chauve, la première a été la création du Parc National de Souss-Massa (PNSM) en 1991 ...

  4. The World Bank | CRDI - Centre de recherches pour le ...

    International Development Research Centre (IDRC) Digital Library (Canada)

    Accueil · Ce que nous faisons · Nos partenaires et initiatives. The World Bank. The World Bank. http://www.worldbank.org/ · Ce que nous faisons · Financement · Ressources · À propos du CRDI. Savoir. Innovation. Solutions. Carrières · Communiquez avec nous · Plan du site. Abonnez-vous à notre bulletin pour recevoir les ...

  5. Publications | Page 181 | CRDI - Centre de recherches pour le ...

    International Development Research Centre (IDRC) Digital Library (Canada)

    Economic Liberalization and Political Violence : Utopia or Dystopia ? Un ouvrage essentiel pour quiconque souhaite comprendre les conflits et le développement au XXIe siècle. James Putzel, Crisis States Research Centre, London School of Economics. Alors que certains voient en la mondialisation un outil de ...

  6. Publications | Page 186 | CRDI - Centre de recherches pour le ...

    International Development Research Centre (IDRC) Digital Library (Canada)

    Economic Liberalization and Political Violence : Utopia or Dystopia ? Un ouvrage essentiel pour quiconque souhaite comprendre les conflits et le développement au XXIe siècle. James Putzel, Crisis States Research Centre, London School of Economics. Alors que certains voient en la mondialisation un outil de ...

  7. Publications | Page 2 | CRDI - Centre de recherches pour le ...

    International Development Research Centre (IDRC) Digital Library (Canada)

    Documentaire sur des solutions locales qui permettent d'offrir plus de possibilités d'emploi aux femmes au Rwanda. Quand Nyirangaruye Dancilla a perdu son mari, elle s'est tournée vers la production de vin de banane pour ne pas se retrouver sans ressources. Aujourd'hui, les revenus de cette entreprise permettent à ...

  8. Publications | Page 6 | CRDI - Centre de recherches pour le ...

    International Development Research Centre (IDRC) Digital Library (Canada)

    Documentaire sur des solutions locales qui permettent d'offrir plus de possibilités d'emploi aux femmes au Rwanda. Quand Nyirangaruye Dancilla a perdu son mari, elle s'est tournée vers la production de vin de banane pour ne pas se retrouver sans ressources. Aujourd'hui, les revenus de cette entreprise permettent à ...

  9. Consensus formalisé: recommandations de pratiques cliniques pour ...

    African Journals Online (AJOL)

    Destiné aux praticiens, ce travail collaboratif multinational a pour objectif de fournir 16 recommandations de pratiques cliniques simples, fondées sur les preuves, et adaptées aux conditions de l'exercice médical en Afrique. The Pan African Medical Journal 2016;24. AJOL African Journals Online. HOW TO USE AJOL.

  10. Les perspectives pour une repression efficace des infractions ...

    African Journals Online (AJOL)

    ... afin qu'il dispose de compétences nécessaires à son bon fonctionnement. Nous estimons que pour atteindre cet objectif, il faut nécessairement envisager, ... coherent environmental legislation, an operational and efficient legal framework.

  11. Livres | Page 31 | CRDI - Centre de recherches pour le ...

    International Development Research Centre (IDRC) Digital Library (Canada)

    Asie et du Sud-Est,auraient pu, en principe, partir de la Chine pour se rendre à Singapouren se balançant d'arbre. Maison(s) d'édition : CRDI. ISBN: Épuisé. Couverture du livre Community Assessment of Natural Food Sources of Vitamin A ...

  12. Utilisation des modules ATM pour le projet FP420

    CERN Document Server

    Renaglia, T

    2006-01-01

    Le but de cette note est de résumer les premières caractéristiques de l'intégration de 2 modules ATM pour le projet FP420 (voir note technique EDMS n° 743628) ainsi que la liste des problèmes découverts à ce jour sur l

  13. Malaria - Africa's silent tsunami | CRDI - Centre de recherches pour ...

    International Development Research Centre (IDRC) Digital Library (Canada)

    ... help those in distress was justifiably roused following the Indian Ocean tsunami. ... Now there is a rapid movement to a “culture” or norm of net use. ... At the time, however, virtually all mosquito nets were imported from Asia, ... L'union fait la force : des universités africaines se regroupent pour avoir plus de bande passante.

  14. Publications | Page 74 | CRDI - Centre de recherches pour le ...

    International Development Research Centre (IDRC) Digital Library (Canada)

    environnement en Angola, un bénéficiaire de subvention de longue date du CRDI conjugue des observations obtenues par satellite et des données... Petits bassins individuels pour l'irrigation de complément : analyse diagnostique des bassins ...

  15. De nouveaux vaccins pour animaux pourraient aider davantage d ...

    International Development Research Centre (IDRC) Digital Library (Canada)

    9 juil. 2013 ... Marie-Danielle Smith. Des scientifiques canadiens et africains mettent au point de nouveaux vaccins pour lutter contre les maladies animales et limiter les pertes économiques en Afrique subsaharienne. Certains de ces vaccins pourraient permettre de lutter contre des maladies semblables au Canada.

  16. Asie centrale | Page 77 | CRDI - Centre de recherches pour le ...

    International Development Research Centre (IDRC) Digital Library (Canada)

    Read more about Moyens que prennent les collectivités pour faire face aux souvenirs traumatiques - enseignements tirés d'Aceh et du Timor-Leste. Langue French. Read more about How Communities Deal with Traumatic Memory: Lessons from Aceh and Timor-Leste. Langue English. Read more about Réduction des ...

  17. Des statistiques essentielles | CRDI - Centre de recherches pour le ...

    International Development Research Centre (IDRC) Digital Library (Canada)

    un programme de recherche sur le terrain mené pour le compte du Centre international de recherche sur les maladies diarrhéiques. Au début, les accoucheuses traditionnelles faisaient état de variations démographiques hebdomadaires dans ...

  18. West Bank and Gaza | CRDI - Centre de recherches pour le ...

    International Development Research Centre (IDRC) Digital Library (Canada)

    Much of this research contributes knowledge for local and international players ... for Policy and Survey Research identified a lack of consultation with the public as a ... Une réforme du droit de la famille pour remettre en question la violence ...

  19. Entretien avec Susan Holtz | CRDI - Centre de recherches pour le ...

    International Development Research Centre (IDRC) Digital Library (Canada)

    26 nov. 2010 ... ... Centre de recherches pour le développement international comme l'un des ... Toutefois, le discours public sur l'intégration d'objectifs environnementaux et .... très conservatrice des experts du droit commercial international, ...

  20. Publications | Page 55 | CRDI - Centre de recherches pour le ...

    International Development Research Centre (IDRC) Digital Library (Canada)

    élaboration de sa prochaine stratégie quinquennale, le CRDI a organisé. ... Au cours de la dernière décennie, un certain nombre d'initiatives au Canada ont permis de mettre au point des stratégies et des forums pour permettre la mise en commun ...

  1. Publications | Page 84 | CRDI - Centre de recherches pour le ...

    International Development Research Centre (IDRC) Digital Library (Canada)

    Le CRDI collabore avec les chercheurs et les établissements des pays en développement ... Utilisez cet outil de recherche pour trouver une publication précise liée à votre ... La gestion de la demande en eau, un instrument de justice sociale.

  2. Inde | Page 60 | CRDI - Centre de recherches pour le ...

    International Development Research Centre (IDRC) Digital Library (Canada)

    ... have developed new environmental and community approaches to reduce the ... A study on mobile phone use by the poor has resulted in the cancellation of a ... To kill the germs, people pour water into clear plastic bottles and then leave ...

  3. Inde | Page 90 | CRDI - Centre de recherches pour le ...

    International Development Research Centre (IDRC) Digital Library (Canada)

    However, as entrepreneurs scour the world in search of new commodities, a voice of dissent is growing and striving to be heard. ... entreprises doivent se faire concurrence pour survivre, prendre de l'expansion et occuper une part du marché, les bibliothécaires et les professionnels de l'information doivent jouer un rôle plus ...

  4. Appel à propositions pour le concours de 2018 du Programme ...

    International Development Research Centre (IDRC) Digital Library (Canada)

    23 nov. 2017 ... Zipline uses drone technology to save lives. Sarah Farhat / Banque mondiale. Le CRDI, l'Israel Science Foundation, la Fondation Azrieli et les Instituts de recherche en santé du Canada annoncent l'appel de propositions pour la quatrième ronde du Programme conjoint canado-israélien de recherche en ...

  5. Publications | Page 79 | CRDI - Centre de recherches pour le ...

    International Development Research Centre (IDRC) Digital Library (Canada)

    Le Sri Lanka mieux préparé aux futurs tsunamis. Les collectivités côtières vulnérables du Sri Lanka sont désormais mieux outillées pour survivre aux tsunamis, cyclones et autres catastrophes naturelles survenant soudainement. Ce degré accru de.

  6. Droits d'auteur | CRDI - Centre de recherches pour le ...

    International Development Research Centre (IDRC) Digital Library (Canada)

    Droits d'auteur détenus par le CRDI Sauf indication contraire, les droits d'auteur relatifs aux documents mis en ligne sur le présent site Web sont détenus par le Centre de recherches pour le développement international (CRDI).

  7. À propos du CRDI | CRDI - Centre de recherches pour le ...

    International Development Research Centre (IDRC) Digital Library (Canada)

    Le Centre de recherches pour le développement international (CRDI) finance des travaux de recherche dans les pays en développement afin d'y favoriser la croissance, de réduire la pauvreté et d'impulser des changements positifs à grande échelle.

  8. Publications | Page 103 | CRDI - Centre de recherches pour le ...

    International Development Research Centre (IDRC) Digital Library (Canada)

    Le FIE 2008 fait avancer le cadre écobiosocial de l'OMS. Le Programme spécial de recherche et de formation concernant les maladies tropicales (TDR) de l'OMS a élaboré le concept du champ « écobiosocial », qui combine les perspectives écologiques, biologiques et sociales « pour mieux.

  9. Pouring and running a protein gel by reusing commercial cassettes.

    Science.gov (United States)

    Hwang, Alexander C; Grey, Paris H; Cuddy, Katrina; Oppenheimer, David G

    2012-02-12

    The evaluation of proteins using sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) analysis is a common technique used by biochemistry and molecular biology researchers. For laboratories that perform daily analyses of proteins, the cost of commercially available polyacrylamide gels (~$10/gel) can be considerable over time. To mitigate this cost, some researchers prepare their own polyacrylamide gels. Traditional methods of pouring these gels typically utilize specialized equipment and glass gel plates that can be expensive and preclude pouring many gels and storing them for future use. Furthermore, handling of glass plates during cleaning or gel pouring can result in accidental breakage creating a safety hazard, which may preclude their use in undergraduate laboratory classes. Our protocol demonstrates how to pour multiple protein gels simultaneously by recycling Invitrogen Nupage Novex minigel cassettes, and inexpensive materials purchased at a home improvement store. This economical and streamlined method includes a way to store the gels at 4°C for a few weeks. By re-using the plastic gel cassettes from commercially available gels, labs that run frequent protein gels can save significant costs and help the environment. In addition, plastic gel cassettes are extremely resistant to breakage, which makes them ideal for undergraduate laboratory classrooms.

  10. Poursuivre les travaux en cours pour la lutte antitabac | CRDI ...

    International Development Research Centre (IDRC) Digital Library (Canada)

    29 mai 2017 ... ... présentation de données justifiant les hausses de taxes sur le tabac ... par le CRDI et le Department for International Development (R.-U.). .... Abonnez-vous à notre bulletin pour recevoir les nouvelles du CRDI chaque mois.

  11. Publications | Page 173 | CRDI - Centre de recherches pour le ...

    International Development Research Centre (IDRC) Digital Library (Canada)

    E-Commerce in the Asian Context : Selected Case Studies. Le commerce électronique en Asie retient beaucoup l'attention en raison de la prolifération des connexions Internet et des technologies connexes dans la région. Face à cette tendance, le Centre de recherches pour le développement international (.

  12. Malaisie : tous les projets | CRDI - Centre de recherches pour le ...

    International Development Research Centre (IDRC) Digital Library (Canada)

    Sujet: UNFAIR COMPETITION, COMPETITION POLICY, COMPETITION LAW, CONSUMER PROTECTION. Région: Central Asia, Far East Asia, South Asia, Malaysia, Philippines, Thailand. Programme: Emploi et croissance. Financement total : CA$ 338,100.00. Élaboration de politiques efficaces pour le financement de ...

  13. Publications | Page 133 | CRDI - Centre de recherches pour le ...

    International Development Research Centre (IDRC) Digital Library (Canada)

    Le 28 juin 2006, le domaine de programme Innovation, politique et science (IPS) a présenté au Conseil des gouverneurs du CRDI un plan stratégique pour orienter la phase initiale (2006 2011) des recherches ... Simultanément, il explore certaines des options permettant d'envisager la revitalisation de ce processus.

  14. Longa sobrevida com erlotinib como tratamento de segunda linha do cancro do pulmão de não pequenas células

    Directory of Open Access Journals (Sweden)

    Mariana Sousa

    2008-10-01

    Full Text Available Resumo: Homem, de 69 anos, caucasiano, trabalhador agrícola. Antecedentes de HTA, dislipidemia e exposição a pesticidas; sem hábitos tabágicos nem antecedentes familiares relevantes. Em Outubro/2005 iniciou dispneia e astenia para esforços moderados, tosse seca e pieira nocturna, que manteve apesar de vários tratamentos antibióticos. Em Dezembro/2005, foi encaminhado à urgência do hospital, onde se diagnosticou derrame pleural direito. O estudo do líquido pleural, a broncofibroscopia, a biópsia e os estudos de estadiamento permitiram o diagnóstico: adenocarcinoma pulmonar estádio IIIB (derrame pleural positivo em Dezembro 2005. Fez toracocentese, pleurodese e radioterapia local. Realizou tratamento citostático com protocolo gemcitabina-carboplatina de 16/02/2006 até 13/07/2006 com alguma toxicidade hematológica. A avaliação de resposta demonstrou agravamento da doença, iniciando segunda linha de tratamento com erlotinib 150 mg, em 21/08/2006. Nesta altura, mantém tratamento com erlotinib e estabilidade da doença. Apresenta bom estado geral, sendo o principal efeito secundário do tratamento um rash na face, antebraços e mãos.Rev Port Pneumol 2008; XIV (Supl 3: S83-S86 Abstract: Male, of 69 years old, caucasian, farmer, non smoker, with hypertension, dyslipidemia and past pesticide exposition, without known familiar diseases. In October/2005, he initiated dyspnoea and asthenia for moderate efforts, cough and night sibling, with persisted although several antibiotic treatments were done. In December/2005, he went to the Emergency department, where it was seen a right pleural effusion. The pleural liquid study, the bronchofiberscope examination, the biopsy and the studies for cancer staging allowed the diagnosis: Lung Adenocarcinoma stage IIIB (positive pleural effusion – December 2005. He was submitted to thoracocentesis, pleurodesis and local radiotherapy. He

  15. Novel targeted approaches to treating biliary tract cancer: the dual epidermal growth factor receptor and ErbB-2 tyrosine kinase inhibitor NVP-AEE788 is more efficient than the epidermal growth factor receptor inhibitors gefitinib and erlotinib.

    Science.gov (United States)

    Wiedmann, Marcus; Feisthammel, Jürgen; Blüthner, Thilo; Tannapfel, Andrea; Kamenz, Thomas; Kluge, Annett; Mössner, Joachim; Caca, Karel

    2006-08-01

    Aberrant activation of the epidermal growth factor receptor is frequently observed in neoplasia, notably in tumors of epithelial origin. Attempts to treat such tumors with epidermal growth factor receptor antagonists resulted in remarkable success in recent studies. Little is known, however, about the efficacy of this therapy in biliary tract cancer. Protein expression of epidermal growth factor receptor, ErbB-2, and vascular endothelial growth factor receptor-2 was assessed in seven human biliary tract cancer cell lines by immunoblotting. In addition, histological sections from 19 patients with extrahepatic cholangiocarcinoma were analyzed for epidermal growth factor receptor, ErbB-2 and vascular endothelial growth factor receptor-2 expression by immunohistochemistry. Moreover, we sequenced the cDNA products representing the entire epidermal growth factor receptor coding region of the seven cell lines, and searched for genomic epidermal growth factor receptor amplifications and polysomy by fluorescence in-situ hybridization. Cell growth inhibition by gefitinib erlotinib and NVP-AEE788 was studied in vitro by automated cell counting. In addition, the anti-tumoral effect of erlotinib and NVP-AEE788 was studied in a chimeric mouse model. The anti-tumoral drug mechanism in this model was assessed by MIB-1 antibody staining, terminal deoxynucleotidyl transfer-mediated dUTP nick end-labelling assay, von Willebrand factor staining, and immunoblotting for p-p42/44 (p-Erk1/2, p-MAPK) and p-AKT. Immunoblotting revealed expression of epidermal growth factor receptor, ErbB-2, and vascular endothelial growth factor receptor-2 in all biliary tract cancer cell lines. EGFR was detectable in six of 19 (32%) extrahepatic human cholangiocarcinoma tissue samples, ErbB-2 in 16 of 19 (84%), and vascular endothelial growth factor receptor-2 in nine of 19 (47%). Neither epidermal growth factor receptor mutations nor amplifications or polysomy were found in the seven biliary tract cancer

  16. Big drinkers: how BMI, gender and rules of thumb influence the free pouring of wine.

    Science.gov (United States)

    Smarandescu, Laura; Walker, Doug; Wansink, Brian

    2014-11-01

    This research examines free pouring behavior and provides an account of how Body Mass Index (BMI) and gender might lead to the overpouring, and consequently the overconsumption of wine. An observational study with young adults investigated how BMI and gender affect free-pouring of wine over a variety of pouring scenarios, and how rules-of-thumb in pouring affect the quantities of alcohol poured by men and women across BMI categories. For men, the amount poured was positively related to BMI. However, BMI did not affect pours by women. The use of the "half glass" rule-of-thumb in pouring reduced the volume of wine poured by over 20% for both men and women. Importantly, this rule-of-thumb substantially attenuated the pours by men at high BMI levels. Increasing awareness of pouring biases represents an early and effective step toward curbing alcohol consumption among men, and especially those who are overweight. Additionally, using a simple "half glass" rule-of-thumb may be an effective way to curb overpouring, despite non-standard glass sizes. Copyright © 2014. Published by Elsevier B.V.

  17. Algorithmes et architectures pour ordinateurs quantiques supraconducteurs

    Science.gov (United States)

    Blais, A.

    2003-09-01

    'utilisation de qubits basés sur les jonctions Josephson. On présente entre autres une approche originale pour l'interaction entre qubits. Cette approche est très générale puisqu'elle peut être appliquée à différents designs de qubits. Finalement, on s'intéresse à la lecture des qubits supraconducteurs de flux. Le détecteur suggéré ici a l'avantage de pouvoir être découplé du qubit lorsqu'il n'y a pas de mesure en cours.

  18. Analysis of the DWPF glass pouring system using neural networks

    International Nuclear Information System (INIS)

    Calloway, T.B. Jr.; Jantzen, C.M.

    1997-01-01

    Neural networks were used to determine the sensitivity of 39 selected Melter/Melter Off Gas and Melter Feed System process parameters as related to the Defense Waste Processing Facility (DWPF) Melter Pour Spout Pressure during the overall analysis and resolution of the DWPF glass production and pouring issues. Two different commercial neural network software packages were used for this analysis. Models were developed and used to determine the critical parameters which accurately describe the DWPF Pour Spout Pressure. The model created using a low-end software package has a root mean square error of ± 0.35 inwc ( 2 = 0.77) with respect to the plant data used to validate and test the model. The model created using a high-end software package has a R 2 = 0.97 with respect to the plant data used to validate and test the model. The models developed for this application identified the key process parameters which contribute to the control of the DWPF Melter Pour Spout pressure during glass pouring operations. The relative contribution and ranking of the selected parameters was determined using the modeling software. Neural network computing software was determined to be a cost-effective software tool for process engineers performing troubleshooting and system performance monitoring activities. In remote high-level waste processing environments, neural network software is especially useful as a replacement for sensors which have failed and are costly to replace. The software can be used to accurately model critical remotely installed plant instrumentation. When the instrumentation fails, the software can be used to provide a soft sensor to replace the actual sensor, thereby decreasing the overall operating cost. Additionally, neural network software tools require very little training and are especially useful in mining or selecting critical variables from the vast amounts of data collected from process computers

  19. Tratamento do carcinoma pulmonar de não pequenas células, doença avançada, com erlotinib em segunda e terceira linhas. A propósito de dois casos clínicos

    Directory of Open Access Journals (Sweden)

    Encarnação Teixeira

    2008-10-01

    Full Text Available Resumo: Os agentes inibidores dos receptores de membrana tirosina cinase como o EGFR tem sido um alvo atractivo, visto que o EGFR está sobreexpresso em cerca de 80% dos CPNPC. O erlotinib em monoterapia após falência de pelo menos um esquema de quimio-terapia prévia prolonga a sobrevivência e melhora a qualidade de vida, embora com modesta taxa de resposta. As mulheres, não fumadores, adenocarcinomas e asiáticos estão associados a melhor resposta. É neste grupo de doentes que mais frequentemente se encontra a mutação do EGFR. Os autores descrevem dois casos, com importante controlo sintomático e aumento do tempo para a progressão independente-mente do tipo de resposta à terapêutica (estabilização ou resposta parcial.Rev Port Pneumol 2008; XIV (Supl 3: S53-S60 Abstract: Agents that inhibit the activity of cell membrane receptor tyrosine kinases, such as the human epidermal growth factor receptor (EGFR have been an attractive target because EGFR is expressed by 80% of NSCLC. Erlotinib as monotherapy in the treatment of NSCLC after failure of at least one prior chemotherapy regimen, prolonged survival and improved quality of life, although modest response rate. Women, Asiens, patients with Adenocarcinoma and never smokers, were more likely than other patients to have a response to erlotinib. This is the group of patients that most commonly have an EGFR mutation. The authors describe two cases, with important control of symptoms and increased time to progression, independently o response rate (stable disease or partial response.Rev Port Pneumol 2008; XIV (Supl 3: S53-S60 Palavras-chave: Carcinoma pulmonar de não pequenas células, terapêutica, inibidores do EGFR, erlotinib, Key-words: Non-small cell lung cancer, treatment, EGFR inhibitors, erlotinib

  20. Preclinical PK/PD model for combined administration of erlotinib and sunitinib in the treatment of A549 human NSCLC xenograft mice.

    Science.gov (United States)

    Li, Jing-Yun; Ren, Yu-Peng; Yuan, Yin; Ji, Shuang-Min; Zhou, Shu-Pei; Wang, Li-Jie; Mou, Zhen-Zhen; Li, Liang; Lu, Wei; Zhou, Tian-Yan

    2016-07-01

    Combined therapy of EGFR TKI and VEGFR TKI may produce a greater therapeutic benefit and overcome EGFR TKI-induced resistance. However, a previous study shows that a combination of EGFR TKI erlotinib (ER) with VEGFR TKI sunitinib (SU) did not improve the overall survival in patients with non-small-cell lung cancer (NSCLC). In this study we examined the anticancer effect of ER, SU and their combination in the treatment of A549 human NSCLC xenograft mice, and conducted PK/PD modeling and simulations to optimize the dose regimen. ER (20, 50 mg·kg(-1)·d(-1)) or SU (5, 10, 20 mg·kg(-1)·d(-1)) alone, or their combination were administered to BALB/c nude mice bearing A549 tumors for 22 days. The tumor size and body weight were recorded daily. The experimental data were used to develop PK/PD models describing the quantitative relationship between the plasma concentrations and tumor suppression in different dose regimens. The models were further evaluated and validated, and used to predict the efficacy of different combination regimens and to select the optimal regimen. The in vivo anticancer efficacy of the combination groups was much stronger than that of either drug administered alone. A PK/PD model was developed with a combination index (φ) of 4.4, revealing a strong synergistic effect between ER and SU. The model simulation predicted the tumor growth in different dosage regimens, and showed that the dose of SU played a decisive role in the combination treatment, and suggested that a lower dose of ER (≤5 mg·kg(-1)·d(-1)) and adjusting the dose of SU might yield a better dosage regimen for clinical research. The experimental data and modeling confirm synergistic anticancer effect of ER and SU in the treatment of A549 xenograft mice. The optimal dosage regimen determined by the PK/PD modeling and simulation can be used in future preclinical study and provide a reference for clinical application.

  1. Contribution of EGFR and ErbB-3 Heterodimerization to the EGFR Mutation-Induced Gefitinib- and Erlotinib-Resistance in Non-Small-Cell Lung Carcinoma Treatments.

    Directory of Open Access Journals (Sweden)

    Debby D Wang

    Full Text Available EGFR mutation-induced drug resistance has become a major threat to the treatment of non-small-cell lung carcinoma. Essentially, the resistance mechanism involves modifications of the intracellular signaling pathways. In our work, we separately investigated the EGFR and ErbB-3 heterodimerization, regarded as the origin of intracellular signaling pathways. On one hand, we combined the molecular interaction in EGFR heterodimerization with that between the EGFR tyrosine kinase and its inhibitor. For 168 clinical subjects, we characterized their corresponding EGFR mutations using molecular interactions, with three potential dimerization partners (ErbB-2, IGF-1R and c-Met of EGFR and two of its small molecule inhibitors (gefitinib and erlotinib. Based on molecular dynamics simulations and structural analysis, we modeled these mutant-partner or mutant-inhibitor interactions using binding free energy and its components. As a consequence, the mutant-partner interactions are amplified for mutants L858R and L858R_T790M, compared to the wild type EGFR. Mutant delL747_P753insS represents the largest difference between the mutant-IGF-1R interaction and the mutant-inhibitor interaction, which explains the shorter progression-free survival of an inhibitor to this mutant type. Besides, feature sets including different energy components were constructed, and efficient regression trees were applied to map these features to the progression-free survival of an inhibitor. On the other hand, we comparably examined the interactions between ErbB-3 and its partners (EGFR mutants, IGF-1R, ErbB-2 and c-Met. Compared to others, c-Met shows a remarkably-strong binding with ErbB-3, implying its significant role in regulating ErbB-3 signaling. Moreover, EGFR mutants corresponding to poor clinical outcomes, such as L858R_T790M, possess lower binding affinities with ErbB-3 than c-Met does. This may promote the communication between ErbB-3 and c-Met in these cancer cells. The

  2. Quel contrôle de gestion pour les startups ?

    OpenAIRE

    Meyssonnier , François

    2015-01-01

    Une étude de huit PME fondées sur la science permet d’identifier les spécificités du contrôle de gestion des startups. Dans les startups émergentes le dirigeant n’utilise que des linéaments de contrôle de gestion essentiellement pour développer son approche cognitive du business model. Dans les startups en croissance le contrôle de gestion a un rôle de garde-fou et les outils de pilotage de la performance sont utilisés essentiellement de façon interactive et pour la prévision. Les principaux ...

  3. Publications | Page 14 | CRDI - Centre de recherches pour le ...

    International Development Research Centre (IDRC) Digital Library (Canada)

    Le livre 2016 Ciudades de Vida y Muerte: La ville et le pacte social pour la contention de la violence présente une analyse convaincante de la coexistence de la violence et de la corruption Avec compassion et solidarité dans les villes du Venezuela - et les leçons qui peuvent être tirées de leur expérience. Cities of Life and ...

  4. Économies inclusives | CRDI - Centre de recherches pour le ...

    International Development Research Centre (IDRC) Digital Library (Canada)

    Pour faire face à ces problèmes et se préparer au prochain cycle de planification, la plus grande agence de planification économique de la Chine a invité la Banque asiatique de développement (BAD) à entreprendre des recherches afin d'éclairer le plan quinquennal 2016-2020 du pays. Read more about Chine : un ...

  5. Inde | Page 107 | CRDI - Centre de recherches pour le ...

    International Development Research Centre (IDRC) Digital Library (Canada)

    S'il se peut bien que les changements climatiques viennent aggraver le problème, il ressort de recherches menées dans deux bassins versants du sud du pays que la pollution industrielle, l'exploitation non réglementée des ressources et les changements d'utilisation des terres sont les principales menaces pour la qualité ...

  6. Partenaires et initiatives | CRDI - Centre de recherches pour le ...

    International Development Research Centre (IDRC) Digital Library (Canada)

    Les frontières s'effacent lorsqu'il s'agit de problèmes tels que les changements climatiques, les maladies infectieuses, la pauvreté et l'instabilité. De nos jours, les difficultés auxquelles font face les pays en voie de développement nous touchent tous. Pour traiter ces problèmes, il faut une intervention internationale ...

  7. Le Conseil des gouverneurs | CRDI - Centre de recherches pour le ...

    International Development Research Centre (IDRC) Digital Library (Canada)

    Le Conseil des gouverneurs guide le travail du CRDI en lui fournissant une orientation stratégique, en examinant ses activités et en approuvant ses budgets. Les gouverneurs – un maximum de 14 – sont nommés par le gouverneur en conseil du Canada pour un mandat d'au plus quatre ans, qui peut être reconduit. La Loi ...

  8. Désabonnez-vous | CRDI - Centre de recherches pour le ...

    International Development Research Centre (IDRC) Digital Library (Canada)

    Abonnez-vous à notre bulletin pour recevoir les nouvelles du CRDI chaque mois. Abonnez-vous · Droits d'auteur · Éthique de la recherche · Politique de libre accès · Politique de confidentialité · Transparence · Utilisation du site Web. Suivez-nous; Facebook · Twitter · Youtube · Linked In · RSS Feed. © 2015 CRDI.

  9. Abonnez-vous | CRDI - Centre de recherches pour le ...

    International Development Research Centre (IDRC) Digital Library (Canada)

    Abonnez-vous à notre bulletin pour recevoir les nouvelles du CRDI chaque mois. Abonnez-vous · Droits d'auteur · Éthique de la recherche · Politique de libre accès · Politique de confidentialité · Transparence · Utilisation du site Web. Suivez-nous; Facebook · Twitter · Youtube · Linked In · RSS Feed. © 2015 CRDI.

  10. Des effets durables : Asie | CRDI - Centre de recherches pour le ...

    International Development Research Centre (IDRC) Digital Library (Canada)

    6 juin 2014 ... Le Projet hippocampe devient un important protagoniste de la conservation de la faune marine. En savoir plus. L'Initiative pour les micronutriments : des solutions durables à la faim inapparente · L'information améliore les conditions de vie dans les Philippines · De l'eau potable dans les foyers grâce à un ...

  11. Kathryn Touré | CRDI - Centre de recherches pour le ...

    International Development Research Centre (IDRC) Digital Library (Canada)

    Carrières · Communiquez avec nous · Plan du site. Abonnez-vous à notre bulletin pour recevoir les nouvelles du CRDI chaque mois. Abonnez-vous · Droits d'auteur · Éthique de la recherche · Politique de libre accès · Politique de confidentialité · Transparence · Utilisation du site Web. Suivez-nous; Facebook · Twitter ...

  12. Dominique Corti | CRDI - Centre de recherches pour le ...

    International Development Research Centre (IDRC) Digital Library (Canada)

    Carrières · Communiquez avec nous · Plan du site. Abonnez-vous à notre bulletin pour recevoir les nouvelles du CRDI chaque mois. Abonnez-vous · Droits d'auteur · Éthique de la recherche · Politique de libre accès · Politique de confidentialité · Transparence · Utilisation du site Web. Suivez-nous; Facebook · Twitter ...

  13. Margaret Biggs | CRDI - Centre de recherches pour le ...

    International Development Research Centre (IDRC) Digital Library (Canada)

    Carrières · Communiquez avec nous · Plan du site. Abonnez-vous à notre bulletin pour recevoir les nouvelles du CRDI chaque mois. Abonnez-vous · Droits d'auteur · Éthique de la recherche · Politique de libre accès · Politique de confidentialité · Transparence · Utilisation du site Web. Suivez-nous; Facebook · Twitter ...

  14. Sophie D'Amours | CRDI - Centre de recherches pour le ...

    International Development Research Centre (IDRC) Digital Library (Canada)

    Carrières · Communiquez avec nous · Plan du site. Abonnez-vous à notre bulletin pour recevoir les nouvelles du CRDI chaque mois. Abonnez-vous · Droits d'auteur · Éthique de la recherche · Politique de libre accès · Politique de confidentialité · Transparence · Utilisation du site Web. Suivez-nous; Facebook · Twitter ...

  15. Dominique Charron | CRDI - Centre de recherches pour le ...

    International Development Research Centre (IDRC) Digital Library (Canada)

    Carrières · Communiquez avec nous · Plan du site. Abonnez-vous à notre bulletin pour recevoir les nouvelles du CRDI chaque mois. Abonnez-vous · Droits d'auteur · Éthique de la recherche · Politique de libre accès · Politique de confidentialité · Transparence · Utilisation du site Web. Suivez-nous; Facebook · Twitter ...

  16. Sylvain Dufour | CRDI - Centre de recherches pour le ...

    International Development Research Centre (IDRC) Digital Library (Canada)

    Carrières · Communiquez avec nous · Plan du site. Abonnez-vous à notre bulletin pour recevoir les nouvelles du CRDI chaque mois. Abonnez-vous · Droits d'auteur · Éthique de la recherche · Politique de libre accès · Politique de confidentialité · Transparence · Utilisation du site Web. Suivez-nous; Facebook · Twitter ...

  17. Joanne Charette | CRDI - Centre de recherches pour le ...

    International Development Research Centre (IDRC) Digital Library (Canada)

    Carrières · Communiquez avec nous · Plan du site. Abonnez-vous à notre bulletin pour recevoir les nouvelles du CRDI chaque mois. Abonnez-vous · Droits d'auteur · Éthique de la recherche · Politique de libre accès · Politique de confidentialité · Transparence · Utilisation du site Web. Suivez-nous; Facebook · Twitter ...

  18. Mary Anne Chambers | CRDI - Centre de recherches pour le ...

    International Development Research Centre (IDRC) Digital Library (Canada)

    Carrières · Communiquez avec nous · Plan du site. Abonnez-vous à notre bulletin pour recevoir les nouvelles du CRDI chaque mois. Abonnez-vous · Droits d'auteur · Éthique de la recherche · Politique de libre accès · Politique de confidentialité · Transparence · Utilisation du site Web. Suivez-nous; Facebook · Twitter ...

  19. Histoires d'Adaptation | CRDI - Centre de recherches pour le ...

    International Development Research Centre (IDRC) Digital Library (Canada)

    29 mars 2011 ... les dynamiques organisationnelles des communautés de base,; l'accès ... transformations dans le mode de gestion du bétail,; la diversification ... L'Afrique de l'Ouest représente un marché lucratif pour l'industrie ... Dans les années 1980, conformément aux recommandations d'organismes internationaux, ...

  20. Publications | Page 45 | CRDI - Centre de recherches pour le ...

    International Development Research Centre (IDRC) Digital Library (Canada)

    Le projet initié par l''ONG Initiatives pour un Développement durable (IDID) " Renforcement des connaissances économiques et de la capacité d''adaptation face aux changements climatiques au Bénin " (PRECAB) vise à améliorer la capacité d''adaptation et la résilience des communautés locales afin.

  1. Publications | Page 46 | CRDI - Centre de recherches pour le ...

    International Development Research Centre (IDRC) Digital Library (Canada)

    Le projet initié par l''ONG Initiatives pour un Développement durable (IDID) " Renforcement des connaissances économiques et de la capacité d''adaptation face aux changements climatiques au Bénin " (PRECAB) vise à améliorer la capacité d''adaptation et la résilience des communautés locales afin.

  2. Communications en cas de catastrophe faisant appel aux TIC pour ...

    International Development Research Centre (IDRC) Digital Library (Canada)

    Communications en cas de catastrophe faisant appel aux TIC pour les collectivités vulnérables des Caraïbes. De récents événements survenus dans les Caraïbes ont mis en relief les insuffisances des mesures régionales et nationales de préparation aux catastrophes. On manque particulièrement de systèmes d'alerte ...

  3. Communiquer les découvertes scientifiques pour initier le ...

    International Development Research Centre (IDRC) Digital Library (Canada)

    La radio est un moyen efficace de faire passer de l'information qui incitera les petits agriculteurs de l'Afrique subsaharienne à adopter des technologies agricoles. Ce projet s'appuiera sur des campagnes radio pour accélérer la mise en oeuvre et l'adoption d'innovations prometteuses en matière d'agriculture et de sécurité ...

  4. Publications | Page 8 | CRDI - Centre de recherches pour le ...

    International Development Research Centre (IDRC) Digital Library (Canada)

    Les économistes et les spécialistes en sciences sociales ont vigoureusement plaidé en faveur d'un revenu de base pour les populations de l'Inde. Entre el activismo y la intervención: El trabajo de organizaciones de la sociedad civil y su incidencia para la salud de mujeres indígenas en México. Le présent ouvrage ...

  5. Myanmar : tous les projets | CRDI - Centre de recherches pour le ...

    International Development Research Centre (IDRC) Digital Library (Canada)

    Una Hakika : Porter à grande échelle les solutions numériques pour la gestion des conflits au Kenya et en Birmanie. Projet. L'information erronée, qu'elle soit le fruit de rumeurs ou d'une désinformation intentionnelle, peut alimenter le conflit et exercer de profondes répercussions sur la paix, la sécurité et la gouvernance ...

  6. Consolider les preuves scientifiques pour faciliter l'orientation des ...

    International Development Research Centre (IDRC) Digital Library (Canada)

    Carrières · Communiquez avec nous · Plan du site. Abonnez-vous à notre bulletin pour recevoir les nouvelles du CRDI chaque mois. Abonnez-vous · Droits d'auteur · Éthique de la recherche · Politique de libre accès · Politique de confidentialité · Transparence · Utilisation du site Web. Suivez-nous; Facebook · Twitter ...

  7. Agriculture et environnement | CRDI - Centre de recherches pour le ...

    International Development Research Centre (IDRC) Digital Library (Canada)

    Par l'entremise de son programme Agriculture et sécurité alimentaire, le CRDI a investi plus de 179 millions de dollars canadiens de 2009 à 2015, pour élaborer, mettre à l'essai et appliquer à grande échelle des solutions qui améliorent la sécurité alimentaire et la nutrition dans les pays en développement. Read more ...

  8. Évaluation organisationnelle | CRDI - Centre de recherches pour le ...

    International Development Research Centre (IDRC) Digital Library (Canada)

    28 oct. 2011 ... Charles Lusthaus, Gary Anderson, Marie-Hélène Adrien et Elaine Murphy (CRDI 1995). Autres outils et ressources. Le site Web Reflect & Learn a vu le jour grâce à Universalia, au Center for Educational Leadership de l'Université McGill et au CRDI. Il a pour but d'améliorer l'évaluation organisationnelle ...

  9. INSP : initiatives et partenariats | CRDI - Centre de recherches pour ...

    International Development Research Centre (IDRC) Digital Library (Canada)

    10 mai 2011 ... L'Institut Nacional de Salud Pública (INSP) du Mexique a accueilli le Forum international écosanté 2008 (FIE 2008) à Mérida. C'était un rôle tout à fait naturel à bien des égards pour l'INSP.La démarche écosanté est le modus operandi que l'institut aimerait adopter, selon Mario-Henry Rodriguez, directeur ...

  10. Peru : tous les projets | CRDI - Centre de recherches pour le ...

    International Development Research Centre (IDRC) Digital Library (Canada)

    Les régimes à teneur élevée en sel sont une cause majeure de l'hypertension artérielle et un facteur prédominant des décès, et comptent pour près des deux tiers des accidents vasculaires cérébraux et de la moitié des incidents de maladie cardiaque dans le monde. Région: Argentina, Brazil, Costa Rica, Paraguay, Peru.

  11. Brazil : tous les projets | CRDI - Centre de recherches pour le ...

    International Development Research Centre (IDRC) Digital Library (Canada)

    Les régimes à teneur élevée en sel sont une cause majeure de l'hypertension artérielle et un facteur prédominant des décès, et comptent pour près des deux tiers des accidents vasculaires cérébraux et de la moitié des incidents de maladie cardiaque dans le monde. Région: Argentina, Brazil, Costa Rica, Paraguay, Peru.

  12. Publications | Page 112 | CRDI - Centre de recherches pour le ...

    International Development Research Centre (IDRC) Digital Library (Canada)

    Le sans fil, un outil de gestion des ressources au Mozambique. Au Mozambique, il faut aimer la solitude pour être garde forestier ou garde-chasse, un métier parfois dangereux. L'année dernière, par exemple, un garde-chasse a essuyé le feu d'un braconnier dans une nouvelle réserve naturelle de la.

  13. Centre de recherches pour le développement international ...

    International Development Research Centre (IDRC) Digital Library (Canada)

    André Lavoie

    Centre de recherches pour le développement international. Règlement institutionnel. Approuvé par le Comité exécutif de la haute direction. - 1 -. Version 3.0.0 en vigueur le 15-10-2015. Conférences et événements. 1. Contexte. 2. Objectif. 3. Application. 4. Définitions. 5. Rôles et responsabilités. 5.1. Employés. 5.2.

  14. SECTION 4 : BUDGET Remarque : Pour en savoir plus sur les ...

    International Development Research Centre (IDRC) Digital Library (Canada)

    (anonymous)

    SECTION 4 : BUDGET. Remarque : Pour en savoir plus sur les restrictions budgétaires, consulter l'appel à propositions et la foire aux questions. Inscrire toutes les sommes en dollars canadiens. 4.1 Indiquez toutes les dépenses prévues (en CAD). Inscrire une valeur numérique sans caractères, ni espaces, ni virgules (p. ex ...

  15. Global Partners, un programme de petites subventions pour les ...

    International Development Research Centre (IDRC) Digital Library (Canada)

    Le CRDI lance un nouveau projet dans la région de l'ANASE. L'honorable Chrystia Freeland, ministre du Commerce international, a annoncé le lancement d'un nouveau projet financé par le Centre de recherches pour le développement international (CRDI). Voir davantageLe CRDI lance un nouveau projet dans la région ...

  16. Publications | Page 75 | CRDI - Centre de recherches pour le ...

    International Development Research Centre (IDRC) Digital Library (Canada)

    ... techniques de télédétection novatrices permettent de rendre compte de la pauvreté en Angola. Pour mesurer les répercussions de la croissance rapide des bidonvilles sur l'environnement en Angola, un bénéficiaire de subvention de longue date du CRDI conjugue des observations obtenues par satellite et des données.

  17. Publications | Page 74 | CRDI - Centre de recherches pour le ...

    International Development Research Centre (IDRC) Digital Library (Canada)

    ... techniques de télédétection novatrices permettent de rendre compte de la pauvreté en Angola. Pour mesurer les répercussions de la croissance rapide des bidonvilles sur l'environnement en Angola, un bénéficiaire de subvention de longue date du CRDI conjugue des observations obtenues par satellite et des données.

  18. Publications | Page 76 | CRDI - Centre de recherches pour le ...

    International Development Research Centre (IDRC) Digital Library (Canada)

    ... techniques de télédétection novatrices permettent de rendre compte de la pauvreté en Angola. Pour mesurer les répercussions de la croissance rapide des bidonvilles sur l'environnement en Angola, un bénéficiaire de subvention de longue date du CRDI conjugue des observations obtenues par satellite et des données.

  19. Favoriser l'entrepreneuriat | CRDI - Centre de recherches pour le ...

    International Development Research Centre (IDRC) Digital Library (Canada)

    10 avr. 2014 ... Pour comprendre les entrepreneurs d'aujourd'hui, il suffit de s'en remettre au Global Entrepreneurship Monitor (GEM). Lancé en 1999, le projet GEM constitue la plus longue étude sur l'entrepreneuriat au monde; elle s'appuie sur les travaux de plus de 300 chercheurs dans 99 pays. Dans ses enquêtes ...

  20. Supprimer les obstacles pour renforcer l'autonomie des femmes ...

    International Development Research Centre (IDRC) Digital Library (Canada)

    1 févr. 2011 ... Ratna Kapur fait observer qu'en plus du protocole novateur contre la traite des personnes rattaché à la Convention de l'ONU contre la criminalité ... Elle cite une déclaration dans laquelle le Fonds de développement des Nations Unies pour la femme (UNIFEM) affirme que c'est au Bangladesh que la ...

  1. Publications | Page 179 | CRDI - Centre de recherches pour le ...

    International Development Research Centre (IDRC) Digital Library (Canada)

    Hisham Zerriffi n'a aucun mal à énumérer les bienfaits de l'électrification des zones rurales : une meilleure éducation, puisque les enfants ont de la lumière pour lire et étudier, de meilleurs établissements de santé, de meilleurs... La cartographie des incidences : Intégrer l'apprentissage et la réflexion dans les programmes ...

  2. Publications | Page 179 | CRDI - Centre de recherches pour le ...

    International Development Research Centre (IDRC) Digital Library (Canada)

    Le rôle de l'énergie dans le développement rural. Hisham Zerriffi n'a aucun mal à énumérer les bienfaits de l'électrification des zones rurales : une meilleure éducation, puisque les enfants ont de la lumière pour lire et étudier, de meilleurs établissements de santé, de meilleurs.

  3. Publications | Page 177 | CRDI - Centre de recherches pour le ...

    International Development Research Centre (IDRC) Digital Library (Canada)

    Le rôle de l'énergie dans le développement rural. Hisham Zerriffi n'a aucun mal à énumérer les bienfaits de l'électrification des zones rurales : une meilleure éducation, puisque les enfants ont de la lumière pour lire et étudier, de meilleurs établissements de santé, de meilleurs.

  4. Tanzanie | Page 11 | CRDI - Centre de recherches pour le ...

    International Development Research Centre (IDRC) Digital Library (Canada)

    Photo : AIMS. Dans la lutte contre le virus Ebola, les mathématiques sont l'arme de Martial Ndeffo. Cet épidémiologiste camerounais aide le ministère de la Santé du Liberia, engagé dans une course contre la montre pour mettre un frein à la propagation du virus, à prendre des décisions qui auront des incidences sur nous ...

  5. Livres | Page 32 | CRDI - Centre de recherches pour le ...

    International Development Research Centre (IDRC) Digital Library (Canada)

    Couverture du livre GIS for Health and the Environment. GIS for Health and the Environment. La recherche présentée dans cet ouvrage démontre comment on utilise des données de SIG pour illustrer des relations de cause à effet entre les conditions de l'environnement et la santé. Maison(s) d'édition : CRDI. ISBN: Épuisé.

  6. Mechanical pumps for liquid metals; Pompes mecaniques pour metaux liquides

    Energy Technology Data Exchange (ETDEWEB)

    Baumier, J; Gollion, H J [Commissariat a l' Energie Atomique, Fontenay-aux-Roses (France). Centre d' Etudes Nucleaires

    1964-07-01

    The pumping of liquid metals by centrifugal pumps poses two principal problems. These are hermetic sealing of the rotating shaft and, its guidance where immersed in liquid metal. The solutions to the problems used on 13 experimental pumps are given here. The resolution of the guidance problem consists in the majority of cases in the utilisation of hydrostatic bearings. Accordingly, a theoretical study was instituted for the first time to calculate the bearings of the earlier pumps. After this, an experimental study was carried out, to check the theory by water tests. A relation for bearing calculation of pumps with diffusers is proposed. Finally the influence of the bearing elasticity on the shafts critical speed is studied. (authors) [French] Le pompage des metaux liquides, par des pompes centrifuges, pose 2 principaux problemes, qui sont: d'une part, la realisation d'une excellente etancheite au passage de l'arbre, d'autre part, son guidage sur la partie immergee dans le metal liquide. Les solutions retenues pour resoudre ces problemes sur 13 pompes experimentees sont presentees. Le probleme du guidage de l'arbre, a dans la majorite des cas ete resolu en utilisant un palier hydrostatique, aussi l'etude en a d'abord ete approfondie de facon theorique pour calculer les paliers des premieres pompes, puis experimentale pour controler la theorie, en effectuant des essais a l'eau. On propose une relation pour calculer les paliers des pompes a diffuseurs. On a en outre effectue une etude de l'influence de l'elasticite du palier hydrostatique sur la vitesse critique de l'arbre. (auteurs)

  7. Publications | Page 222 | CRDI - Centre de recherches pour le ...

    International Development Research Centre (IDRC) Digital Library (Canada)

    Transport et réduction de la pauvreté : étude de cas sur la contribution du secteur des transports à la réalisation des Objectifs du Millénaire pour le Développement (Burkina Faso) (restricted access). Le Burkina Faso, comme la plupart des pays en développement, est confronté à des problèmes liés à l''aggravation de la ...

  8. Publications | Page 156 | CRDI - Centre de recherches pour le ...

    International Development Research Centre (IDRC) Digital Library (Canada)

    ... and Community Diversity. La mer des Caraïbes est la deuxième au monde pour sa superficie et sa région englobe plus de 30 pays insulaires et continentaux où vivent près de 35 millions d'habitants. Outre son territoire fragmenté, cette région se caractérise par sa grande diversité linguistique et culturelle, ce phénomène.

  9. Les splenectomies pour rate non traumatique en milieu tropical ...

    African Journals Online (AJOL)

    La pathologie de la rate non traumatique est fréquente et nécessite parfois la réalisation d'une splénectomie préventive, diagnostique ou thérapeutique. But: analyser les indications thérapeutiques des splénectomies pour la rate non traumatique et évaluer les suites opératoires à moyen terme. Méthode: Etude ...

  10. Recommandations pour une agriculture plus écologique respectant ...

    African Journals Online (AJOL)

    Dans le Menabe Central (côte ouest de Madagascar), les paysages forestiers deviennent toujours plus ouverts, le taux de déforestation avoisinant les 0,7 % . La déforestation étant notamment due à des défrichements pour l'agriculture qui est la principale activité de la région, une gestion agricole écologiquement durable ...

  11. Solution volumes finis polynomiale par morceaux pour les ...

    African Journals Online (AJOL)

    Nous présentons dans ce papier un concept de solution volumes finis continue pour des problèmes de diffusion-convection avec des données régulières. Nous comparons dans certains cas particuliers la solution proposée avec la solution volumes finis classiques (qui est une fonction constante par morceaux) et la ...

  12. Publications | Page 213 | CRDI - Centre de recherches pour le ...

    International Development Research Centre (IDRC) Digital Library (Canada)

    Projet de recherche : gouvernance et qualité des soins au Bénin; rapport final de recherche (restricted access). Dans le cadre de l''objectif social de l''OMS " Santé pour tous ", les pays africains comme le Bénin ont entrepris des reformes de leur système de santé avec la décentralisation des structures de soins et la mise en ...

  13. Publications | Page 111 | CRDI - Centre de recherches pour le ...

    International Development Research Centre (IDRC) Digital Library (Canada)

    Technologie et langue : apprendre à dire souris en kiché. Quand, dès l'âge de la maternelle, des enfants s'assoient pour la première fois devant un ordinateur équipé d'un logiciel en kiché, leur langue maternelle maya, les leçons dépassent de loin la maîtrise de connaissances élémentaires en.

  14. Publications | Page 94 | CRDI - Centre de recherches pour le ...

    International Development Research Centre (IDRC) Digital Library (Canada)

    Le CRDI collabore avec les chercheurs et les établissements des pays en développement au renforcement des capacités locales par le truchement du financement, ... Le syndrome... Diamants de guerre — pour en finir. L'important accord international sur les diamants conclu cette année ne portera pas fruits s'il n'est pas ...

  15. Publications | Page 39 | CRDI - Centre de recherches pour le ...

    International Development Research Centre (IDRC) Digital Library (Canada)

    Pour des villes d'Amérique centrale plus sécuritaires : Réaction de la communauté au crime et à la violence. Pourquoi les villes où il existe des conditions d'exclusion sociale similaires présentent-elles des degrés de violence différents? Des chercheurs du Costa Rica et du Salvador, soutenus par le CRDI, communiquent ...

  16. Inde | Page 116 | CRDI - Centre de recherches pour le ...

    International Development Research Centre (IDRC) Digital Library (Canada)

    Le Programme d'action de Beijing visait à rendre toutes les femmes autonomes. Mais avons-nous perdu quelque chose dans les batailles considérées comme remportées ? Et qu'avons-nous gagné dans les batailles considérées comme perdues ? Read more about Supprimer les obstacles pour renforcer l'autonomie des ...

  17. Livres | Page 17 | CRDI - Centre de recherches pour le ...

    International Development Research Centre (IDRC) Digital Library (Canada)

    Accountability of the International Monetary Fund. La question de la responsabilisation est au cœur du débat sur la réforme du FMI. Malheureusement, il s'agit d'un sujet pour lequel l'analyse est trop souvent entachée de jugements de valeur. Directeur(s) : Barry Carin et Angela Wood. Maison(s) d'édition : Ashgate, CRDI.

  18. Publications | Page 128 | CRDI - Centre de recherches pour le ...

    International Development Research Centre (IDRC) Digital Library (Canada)

    Estimation des élasticités de la demande des céréales sèches et du niébé au Niger à l'aide d'un modèle AIDS (Almost Ideal Demand System) (restricted access). Les mil et sorgho sont les cultures les plus importantes au Niger. Elles occupent plus de 80% des superficies cultivées, comptent pour 5.154.214 tonnes de la ...

  19. Publications | Page 132 | CRDI - Centre de recherches pour le ...

    International Development Research Centre (IDRC) Digital Library (Canada)

    Estimation des élasticités de la demande des céréales sèches et du niébé au Niger à l'aide d'un modèle AIDS (Almost Ideal Demand System) (restricted access). Les mil et sorgho sont les cultures les plus importantes au Niger. Elles occupent plus de 80% des superficies cultivées, comptent pour 5.154.214 tonnes de la ...

  20. Tanzanie | Page 39 | CRDI - Centre de recherches pour le ...

    International Development Research Centre (IDRC) Digital Library (Canada)

    Cinq ans après avoir remis en service ses premiers ordinateurs recyclés et leur avoir trouvé un nouveau nid, l'organisation non gouvernementale Computers ... la participation des collectivités et des responsables locaux aux principales décisions et aux efforts déployés pour améliorer les services de santé peut améliorer le ...

  1. Gestion du Centre | CRDI - Centre de recherches pour le ...

    International Development Research Centre (IDRC) Digital Library (Canada)

    Le Comité de gestion du Centre (CGC) est composé des membres de la haute direction du CRDI, notamment les directeurs de nos quatre bureaux régionaux et de nos principaux secteurs de programme. Le CGC travaille en collaboration avec le président afin de soutenir la recherche pour le développement, lui fournissant ...

  2. Influence of delayed pouring on irreversible hydrocolloid properties

    Directory of Open Access Journals (Sweden)

    Stéfani Becker Rodrigues

    2012-10-01

    Full Text Available The aim of this study was to evaluate the physical properties of irreversible hydrocolloid materials poured immediately and after different storage periods. Four alginates were tested: Color Change (Cavex; Hydrogum (Zhermack; Hydrogum 5 (Zhermack; and Hydro Print Premium (Coltene. Their physical properties, including the recovery from deformation (n = 3, compressive strength (n = 3, and detail reproduction and gypsum compatibility (n = 3, were analyzed according to ANSI/ADA specification no. 18. Specimens were stored at 23ºC and humidity and were then poured with gypsum immediately and after 1, 2, 3, 4, and 5 days. The data were analyzed by two-way analysis of variance (ANOVA and Tukey's test at p < 0.05. All of the alginate impression materials tested exhibited detail reproduction and gypsum compatibility at all times. Hydro Print Premium and Hydrogum 5 showed recovery from deformation, as established by ANSI/ADA specification no. 18, after 5 days of storage. As the storage time increased, the compressive strength values also increased. Considering the properties of compounds' recovery from deformation, compressive strength, and detail reproduction and gypsum compatibility, irreversible hydrocolloids should be poured immediately.

  3. Big Bang pour le grand public - French version only

    CERN Multimedia

    2004-01-01

    Pour commémorer les 50 ans du CERN et l'année de la physique en 2005, la section de physique de l'Université de Genève ouvre une fois de plus ses portes aux non initiés et organise une série de conférences de vulgarisation scientifique. La première conférence, le 7 décembre prochain aura pour thème le Big-Bang et les observations qui corroborent cette théorie. Le Professeur Georges Meylan, Directeur du Laboratoire d'Astrophysique de l'EPFL, donnera cette conférence destinée à tous les publics. Chacune des conférences débutera par une démonstration de détection de rayons cosmiques dans l'auditoire et l'utilisation de ces signaux venus du fond de l'univers pour créer une ?musique cosmique', en collaboration avec le Professeur Ellberger et Nikolai Mihailov du conservatoire de musique de Genève. Ces processus cosmiques étant aléatoires, chacun de ces concerts sera unique. Les preuves observationnelles du Big Bang par le Professeur Georges Meylan Directeur du Laboratoire d'Astrophysique ...

  4. Éléments finis pour les fluides incompressibles

    CERN Document Server

    Azaïez, Mejdi; Mund, Ernest

    2011-01-01

    Cet ouvrage présente l'ensemble des concepts et méthodes nécessaires à la modélisation numérique par éléments finis du comportement des fluides visqueux newtoniens incompressibles. Après un bref rappel des équations de base et des modèles simplifiés, il expose en détail les techniques d'approximation de ces équations par éléments finis pour les dépendances spatiale et temporelle (problèmes de diffusion, d'advection-diffusion et de transport). Une attention toute particulière est portée à la discrétisation spatiale des équations de Stokes et aux algorithmes temporels pour la simulation numérique directe des équations de Navier-Stokes. Un chapitre ancillaire résume les méthodes de résolution des systèmes algébriques de grande taille à structure creuse, caractéristiques des méthodes d'éléments finis. L'exposé clair, didactique et progressif offre un contenu équilibré entre théorie et pratique. Ce manuel constitue ainsi une référence indispensable pour les étudiants de ma...

  5. Carrières | CRDI - Centre de recherches pour le développement ...

    International Development Research Centre (IDRC) Digital Library (Canada)

    Le CRDI regroupe des gens qui partagent une passion pour la recherche pour le développement international. La recherche pour le développement contribue réellement à changer les choses lorsqu'elle reçoit un soutien adéquat et que les bonnes personnes y travaillent. Nous recherchons des personnes qui ont la ferme ...

  6. Tubin, Eduard. Sonate pour violon et piano dans le mode phrygien / Pierre Gervasoni

    Index Scriptorium Estoniae

    Gervasoni, Pierre

    1995-01-01

    Uuest heliplaadist "Tubin, Eduard. Sonate pour violon et piano dans le mode phrygien. Ballade pour piano en forme de Chaconne sur un theme de Mart Saar. Sonate pour saxophone alto et piano. Le Chant des soldats enrepli. Ave Maria. Societe Chorale Estudiantine de Lund, Neeme Järvi. BIS-CD 269, distribution Harmonia Mundi (CD: 161 F), 1984/85.TT: 1h 03'46"

  7. Une plateforme pour la mise au point d'un vaccin anti-adénovirus ...

    International Development Research Centre (IDRC) Digital Library (Canada)

    Une plateforme pour la mise au point d'un vaccin anti-adénovirus non réplicatif contre les maladies aviaires. 09 avril 2018. Fonds d'innovation en vaccins pour le bétail. Photo: Sven Torfinn/Panos Pictures. La volaille constitue un élevage essentiel en Afrique subsaharienne, surtout pour la sécurité alimentaire et ...

  8. Avantages possibles de la téléphonie mobile pour la surveillance ...

    International Development Research Centre (IDRC) Digital Library (Canada)

    Avantages possibles de la téléphonie mobile pour la surveillance épidémiologique au Mali. La charge de morbidité au Mali est l'une des plus lourdes au monde. L'utilisation de téléphones mobiles pour surveiller les flambées de maladies pourrait contribuer à réduire cette charge. La surveillance de la santé publique pour ...

  9. PHASED INCREASE OF SERIAL POURING AT MNLZ-1,2 OF RUP «BMZ» AND PERSPECTIVES OF ITS FURTHER GROWTH

    Directory of Open Access Journals (Sweden)

    M. A. Murikov

    2010-01-01

    Full Text Available Using of gun mixtures for prolonged pouring allowed to increase durability of cindery belts on pouring boxes, however it is necessary to continue matching of refractory bodies, providing long and qualitative pouring.

  10. L’écriture en souffrance pour dire la Shoah

    Directory of Open Access Journals (Sweden)

    Aude Delsescaux

    2010-02-01

    Full Text Available Aujourd’hui la Mémoire de la Shoah est un thème récurrent de notre société. C’est une écriture qui est devenue universelle pour dire le malheur, l’horreur des guerres et des génocides. L’écriture de cette souffrance, les témoignages sont aujourd’hui nombreux et pluriels. Mais quelles sont les enjeux et les raisons de cette ferveur de l’écriture? En outre, l’écriture de la souffrance fut-elle un élément libérateur ou aliénateur pour ces témoins? Par nos recherches nous apprenons qu’il est de coutume pour la «communauté» juive de se souvenir par les livres, par l’écriture. Toutefois cette écriture ne reçut pas tout de suite l’accueil escompté. Après le procès Eichmann, les témoins et leurs récits commencèrent réellement à être entendus. La Mémoire de la Shoah devient alors un élément identitaire européen, permettant aux témoins par l’écriture en souffrance, qu’il s’agisse de romans, de poésies ou de bandes dessinées, de trouver une place dans nos sociétés.

  11. A retrospective analysis of VeriStrat status on outcome of a randomized phase II trial of first-line therapy with gemcitabine, erlotinib, or the combination in elderly patients (age 70 years or older) with stage IIIB/IV non-small-cell lung cancer.

    Science.gov (United States)

    Stinchcombe, Thomas E; Roder, Joanna; Peterman, Amy H; Grigorieva, Julia; Lee, Carrie B; Moore, Dominic T; Socinski, Mark A

    2013-04-01

    In a multicenter randomized phase II trial of gemcitabine (arm A), erlotinib (arm B), and gemcitabine and erlotinib (arm C), similar progression-free survival (PFS) and overall survival (OS) were observed in all arms. We performed an exploratory, blinded, retrospective analysis of plasma or serum samples collected as part of the trial to investigate the ability of VeriStrat (VS) to predict treatment outcomes. Ninety-eight patients were assessable, and the majority had stage IV disease (81%), adenocarcinoma histology (63%), reported current or previous tobacco use (84%), and 26% had a performance status (PS) of 2. In arm A, patients with VS Good (n = 20) compared with VS Poor status (n = 8) had similar PFS (hazard ratio [HR]: 1.21; p = 0.67) and OS (HR: 0.82; p = 0.64). In arm B, patients with VS Good (n = 26) compared with VS Poor (n = 12) had a statistically significantly superior PFS (HR: 0.33; p = 0.002) and OS (HR: 0.40; p = 0.014). In arm C, patients with VS Good (n = 17) compared with Poor (n = 1 5) had a superior PFS (HR: 0.42; p = 0.027) and a trend toward superior OS (HR: 0.48; p = 0.051). In the multivariate analysis for PFS, VS status was statistically significant (p = 0.011); for OS, VS status (p = 0.017) and PS (p = 0.005) were statistically significant. A statistically significant VS and treatment interaction (gemcitabine versus erlotinib) was observed for PFS and OS. Gemcitabine is the superior treatment for elderly patients with VS Poor status. First-line erlotinib for elderly patients with VS Good status may warrant further investigation.

  12. Publications | Page 163 | CRDI - Centre de recherches pour le ...

    International Development Research Centre (IDRC) Digital Library (Canada)

    En Afrique cependant, plus particulièrement pour les femmes vivant en milieu rural, l'accès à l'information est limité. Les nouvelles technologies de l'information et des... Le laboratoire, le temple et le marché : Réflexions à la croisée de la science, de la religion et du développement. Il s'agit là d'un ouvrage fascinant et très ...

  13. Des distinctions internationales | CRDI - Centre de recherches pour ...

    International Development Research Centre (IDRC) Digital Library (Canada)

    3 nov. 2010 ... l'architecte de la révolution verte en Inde, a remporté en 1987 le tout premier Prix mondial de l'alimentation pour avoir fait découvrir aux agriculteurs indiens des variétés de blé et de riz à haut rendement. Le scientifique éthiopien Aklilu Lemma, qui a découvert un molluscicide d'origine végétale pouvant ...

  14. Serge Gruzinski, L’histoire, pour quoi faire ?

    OpenAIRE

    Exbalin, Arnaud

    2015-01-01

    La photographie de Kader Attia qui illustre la couverture du dernier livre de Serge Gruzinski est l’un des nombreux points d’accroche qui jalonnent L’histoire, pour quoi faire ?, un ouvrage qui vient de paraître aux éditions Fayard. Ce cliché d’adolescents algériens jouant au foot dans les ruines romaines de Tazoult vient condenser près de deux mille ans d’histoire, une histoire des colonisations — romaine et française —, une histoire globale qui se manifeste par la pratique d’un sport d’orig...

  15. Affaires mondiales Canada | CRDI - Centre de recherches pour le ...

    International Development Research Centre (IDRC) Digital Library (Canada)

    En tant que société d'État du gouvernement du Canada, nous jouons un rôle important dans les activités du Canada liées aux affaires étrangères et au développement. Nos partenariats appuient la recherche portant sur la santé des mères et des enfants, l'agriculture et la sécurité alimentaire et les données ouvertes pour le ...

  16. Transformations agricoles | CRDI - Centre de recherches pour le ...

    International Development Research Centre (IDRC) Digital Library (Canada)

    13 déc. 2010 ... La région de Souss Massa au centre du Maroc est réputée pour ses fruits et légumes destinés surtout à l'exportation. Toutefois, le manque de pluie chronique dans les régions montagneuses nuit au développement économique et à la santé humaine, car il réduit le rendement de la production et oblige les ...

  17. Plutonium immobilization program - Cold pour Phase 1 test results

    International Nuclear Information System (INIS)

    Hamilton, L.

    2000-01-01

    The Plutonium Immobilization Project will disposition excess weapons grade plutonium. It uses the can-in-canister approach that involves placing plutonium-ceramic pucks in sealed cans that are then placed into Defense Waste Processing Facility canisters. These canisters are subsequently filled with high-level radioactive waste glass. This process puts the plutonium in a stable form and makes it unattractive for reuse. A cold (non-radioactive) glass pour program was performed to develop and verify the baseline design for the canister and internal hardware. This paper describes the Phase 1 scoping test results

  18. Ofelia Floresca-Domingo | CRDI - Centre de recherches pour le ...

    International Development Research Centre (IDRC) Digital Library (Canada)

    Le point culminant du phénomène d'oscillation australe El Niño est survenu en 1997, et les dommages infligés à mon pays ont été très graves. J'ai écrit des articles sur les technologies fondées sur les recherches scientifiques et les recommandations des experts sur la façon pour les Philippins de gérer les effets néfastes ...

  19. egypt : tous les projets | CRDI - Centre de recherches pour le ...

    International Development Research Centre (IDRC) Digital Library (Canada)

    Améliorer les perspectives et les moyens de subsistance pour les communautés marginalisées en Égypte grâce à l'utilisation d'outils numériques ... les institutions religieuses étatiques et les médias publics, et d'évaluer la mesure dans laquelle elles donnent suite aux demandes de réforme formulées dans la foulée du ...

  20. Publications | Page 93 | CRDI - Centre de recherches pour le ...

    International Development Research Centre (IDRC) Digital Library (Canada)

    Lutter contre la pollution de l'air à Mexico. Déclarée ville dont l'atmosphère était la plus polluée de la planète par les Nations Unies en 1992, Mexico se méritait six ans plus tard le titre de « ville la plus dangereuse du monde pour les enfants », une réputation que Mexico s'efforce d'améliorer. Mais, malgré une décennie de ...

  1. Business plan pour une application Smartphone : du concept au lancement

    OpenAIRE

    Vriamont, Gilles

    2015-01-01

    Création d'une application mobile pour Smartphone. Description théorique concernant la rédaction d'un business plan dans une première partie suivi d'une description théorique des caractéristiques des applications mobiles. Dans une seconde partie, analyse de l'industrie des Smartphones et des applications mobiles suivi de la partie pratique et du développement du produit, partant de la description du produit jusqu'à l'analyse des coûts. Master [120] en Ingénieur de gestion, Université catho...

  2. Dessiner ses plans avec QCad le DAO pour tous

    CERN Document Server

    Pascual, André

    2009-01-01

    Logiciel libre de dessin assisté par ordinateur (DAO), QCad permet d'établi dans tous les domaines (architecture dessin industriel, schématique...) de plans rigoureux et normalisés dans un format compris par l'ensemble des logiciels de graphisme. Bien plus accessible qu'AutoCAD en termes de simplicité d'utilisation (et de prix!), il fonctionne sous Windows et Mac OS X aussi bien que sous Linux et allie convivialité et productivité pour convenir au néophyte comme au dessinateur plus aguerri.

  3. Chili : tous les projets | CRDI - Centre de recherches pour le ...

    International Development Research Centre (IDRC) Digital Library (Canada)

    Région: Chile, Colombia, Mexico. Programme: Agriculture et sécurité alimentaire. Financement total : CA$ 5,230,900.00. Le rôle du secteur privé dans la réduction de la corruption en Amérique latine. Projet. Dans le cadre de ce projet, on étudiera les efforts déployés par le secteur privé pour améliorer la conformité aux lois ...

  4. La portee des projets urbains recents pour la grande ville ...

    African Journals Online (AJOL)

    ... mobi-lisé, le potentiel de lisibilité qu'elle recèle pourrait la consolider dans le statut de ville intermédiaire aux échelles nationale et méditerra-néenne. Un statut qu'elle pourrait acquérir à partir d'une triangulation d'actions stratégiques pour consolider la connectivité, créer une syner-gie entre PME/PMI et tourisme, donner ...

  5. Plutonium Immobilization Program - Cold pour Phase 1 test results

    International Nuclear Information System (INIS)

    Hamilton, L.

    2000-01-01

    The Plutonium Immobilization Project will disposition excess weapons grade plutonium. It uses the can-in-canister approach that involves placing plutonium-ceramic pucks in sealed cans that are then placed into Defense Waste Processing Facility canisters. These canisters are subsequently filled with high-level radioactive waste glass. This process puts the plutonium in a stable form and makes it unattractive for reuse. A cold (non-radioactive) glass pour program was performed to develop and verify the baseline design for the canister and internal hardware. This paper describes the Phase 1 scoping test results

  6. Des outils novateurs pour lutter contre les maladies chroniques au ...

    International Development Research Centre (IDRC) Digital Library (Canada)

    29 janv. 2018 ... En dépit des conditions qui compliquent la gestion des MNT, le dépistage et la détection précoces sont d'une grande importance, particulièrement chez les femmes enceintes. Les cas de diabète et d'hypertension, s'ils ne sont pas diagnostiqués et traités, peuvent avoir des effets désastreux pour la mère et ...

  7. Publications | Page 24 | CRDI - Centre de recherches pour le ...

    International Development Research Centre (IDRC) Digital Library (Canada)

    Améliorer les stratégies adaptatives des agriculteurs en intégrant les savoirs endogènes en matière de prévision et d'adaptation climatiques. Les prévisions des services météorologiques du Kenya ont gagné en fiabilité, mais les agriculteurs n'y ont guère recours pour prendre des décisions appropriées relativement à la ...

  8. Session du Conseil du CERN : le ministre britannique, Robert Jackson, souligne l'intérêt de on pays pour l'avenir du CERN : décisions du Conseil pour la mise en oeuvre des recommandations du Comité d'évaluation du CERN: départ anticipé pour 200 membres au moins du personnel - mise à jour de la méthode de calcule pour les contributions des Etats Membres au budget

    CERN Multimedia

    CERN Press Office. Geneva

    1988-01-01

    Session du Conseil du CERN : le ministre britannique, Robert Jackson, souligne l'intérêt de on pays pour l'avenir du CERN : décisions du Conseil pour la mise en oeuvre des recommandations du Comité d'évaluation du CERN: départ anticipé pour 200 membres au moins du personnel - mise à jour de la méthode de calcule pour les contributions des Etats Membres au budget

  9. Ce que nous faisons | Page 41 | CRDI - Centre de recherches pour ...

    International Development Research Centre (IDRC) Digital Library (Canada)

    aflatoxine du maïs et le degré d'exposition pour les humains au Zimbabwe. Ce projet examine des solutions d'après-récolte novatrices pour éviter la contamination du grain par l'aflatoxine. Zimbabwe. PROJECT ...

  10. Pour une meilleure diffusion de l'information scientifique en Afrique ...

    International Development Research Centre (IDRC) Digital Library (Canada)

    7 févr. 2011 ... Soutien aux journalistes scientifiques des pays en développement. Un nouveau programme de mentorat international novateur, qui vise à consolider le ... pour la recherche ( SAREC ) de l'Agence suédoise de coopération internationale pour le ... La recherche fait progresser les droits des femmes arabes.

  11. La cohérence des coalitions interrégionales pour lutter contre le ...

    African Journals Online (AJOL)

    13 avr. 2016 ... et le Bénin à coordonner leur politique d'encadrement sécuritaire pour ..... zones d'opération, des bases arrière, des champs de recrutement, des .... la volonté des pays de se doter d'une stratégie commune pour combattre.

  12. Approche multivalente pour l'amélioration des vaccins inactivés ...

    International Development Research Centre (IDRC) Digital Library (Canada)

    utilisation des terres que le bétail; ils sont donc une source importante de sécurité alimentaire et économique pour ... Une plateforme pour la mise au point d'un vaccin anti-adénovirus non réplicatif contre les maladies aviaires.

  13. Initiative régionale pour la lutte contre le tabac en Afrique ...

    International Development Research Centre (IDRC) Digital Library (Canada)

    Initiative régionale pour la lutte contre le tabac en Afrique - coordination des efforts avec ceux d'organismes africains. Financée par le CRDI et la Fondation Bill et Melinda Gates, l'initiative Analyses situationnelles de la lutte antitabac en Afrique (ASTA) a pour objectif de permettre de comprendre les facteurs déterminants ...

  14. Ghana : tous les projets | Page 4 | CRDI - Centre de recherches pour ...

    International Development Research Centre (IDRC) Digital Library (Canada)

    Sujet: TOBACCO, SMOKING, Disease control, PREVENTIVE MEDICINE, HEALTH POLICY, PROGRAMME EVALUATION. Région: Burkina Faso, Ghana, ... Pour atteindre les objectifs du Millénaire pour le développement d'ici 2015, le Ghana aura besoin d'une aide extérieure considérable. Date de début : 17 mars 2009.

  15. Asie du sud | Page 10 | CRDI - Centre de recherches pour le ...

    International Development Research Centre (IDRC) Digital Library (Canada)

    Langue English. Read more about Comparaison des politiques fiscales et réglementaires pour prévenir les maladies non transmissibles en Inde. Langue French. Read more about Moyens que prennent les collectivités pour faire face aux souvenirs traumatiques - enseignements tirés d'Aceh et du Timor-Leste. Langue ...

  16. Mise en oeuvre de la Convention-cadre pour la lutte antitabac au ...

    International Development Research Centre (IDRC) Digital Library (Canada)

    SEATCA) de coordonner un programme de recherche pour appuyer la mise en oeuvre (dans le cas du Cambodge) et la ratification (dans le cas du Laos) de la Convention-cadre pour la lutte antitabac (CCLAT) de l'Organisation mondiale de la santé.

  17. Sexospécificités | Page 206 | CRDI - Centre de recherches pour le ...

    International Development Research Centre (IDRC) Digital Library (Canada)

    Langue English. La culture illicite du pavot à opium contribue à la subsistance de millions de paysans afghans, mais il se trouve qu'elle constitue également une source de revenus importants pour les bandes criminalisées. Read more about La culture du pavot à opium : quelle politique pour l'Afghanistan ? Langue French.

  18. Ensemble pour apprendre à s'attaquer à de grandes questions de ...

    International Development Research Centre (IDRC) Digital Library (Canada)

    25 janv. 2011 ... Ensemble pour apprendre à s'attaquer à de grandes questions de santé .... pour reprendre l'image de Martin Forde, de l'Université St. George, à la Grenade ... As the world observed International Youth Day (August 12), IDRC ...

  19. Ivermectin excreted in cattle dung after subcutaneous injection or pour-on treatment

    DEFF Research Database (Denmark)

    Sommer, C.; Steffansen, B.; Nielsen, B. Overgaard

    1992-01-01

    Heifers were treated with the recommended doses of ivermectin: 0.2 mg/kg bw by subcutaneous injection or 0.5 mg/kg bw by pour-on. An analytic procedure is described and used for the detection of ivermectin residues excreted in dung. A large amount of the higher pour-on dose was excreted during th...

  20. : tous les projets | Page 47 | CRDI - Centre de recherches pour le ...

    International Development Research Centre (IDRC) Digital Library (Canada)

    La création de zones économiques frontalières constitue une importante stratégie d'industrialisation pour la Thaïlande et ouvre de nouvelles perspectives pour deux de ses pays voisins pauvres, le Cambodge et le Myanmar. Sujet: MIGRANTS. Région: Cambodia, Myanmar, Thailand, Japan. Programme: Employment and ...

  1. Résultats de recherche | Page 8 | CRDI - Centre de recherches pour ...

    International Development Research Centre (IDRC) Digital Library (Canada)

    Initiative régionale pour la lutte contre le tabac en Afrique - coordination des efforts avec ceux d'organismes africains. Financée par le CRDI et la Fondation Bill et Melinda Gates, l'initiative Analyses situationnelles de la lutte antitabac en Afrique (ASTA) a pour objectif de permettre de comprendre les facteurs déterminants ...

  2. La préservation, atout essentiel pour contrer la précarité des ...

    International Development Research Centre (IDRC) Digital Library (Canada)

    La préservation, atout essentiel pour contrer la précarité des moyens de subsistance en ... Union mondiale pour la conservation de la nature et des ressources ... la recherche menée dans les domaines des sciences sociales, des sciences ...

  3. Les mesures de métrologie pour le CLIC

    CERN Document Server

    Cherif, A

    2008-01-01

    Le projet CLIC est en tout point un défi technique majeur ; c?est le cas également pour la mesure dimensionnelle. Quels sont les équipements et les méthodes qui permettent de caractériser les pièces avec une incertitude de mesure aussi réduite que possible, vu les tolérances micrométriques imposées ? Afin de répondre à cette question, une veille technologique a été maintenue sur une longue période. Les acteurs relevants ont été contactés pour bénéficier d?une ouverture sur les dernières avancées dans le domaine. Différentes techniques ont été étudiées et comparées telles que la digitalisation, la tomographie X, la mesure tridimensionnelle. L'assemblage de haute précision des composants est aussi primordial. Sa mise en ?uvre sous un microscope optique ou à l'aide d'une machine tridimensionnelle est en cours d?étude. L'exposé traitera aussi de la mesure de rugosité, un domaine où nous disposons de moyens adaptés aux exigences spécifiques du projet.

  4. Geneva University - Les catégories pour la physique

    CERN Multimedia

    Université de Genève

    2012-01-01

    GENEVA UNIVERSITY Ecole de physique Département de physique nucléaire et corspusculaire 24, quai Ernest-Ansermet 1211 Genève 4 Tél.: (022) 379 62 73 Fax: (022) 379 69 92   Lundi 27 février 2012 17h00 - Auditoire Stueckelberg « Les catégories pour la physique » Marc Lachièze-Rey AstroParticule et Cosmologie Université Paris 7 Diderot, Paris La théorie des catégories est un vaste domaine des mathématiques, que l'on peut comparer à la théorie des ensembles avec une dimension de plus. De nombreuses théories et théorèmes sont (re-)formulés dans ce cadre et certains mathématiciens songent à l'utiliser ce pour refonder la totalité des mathématiques. Catégories et foncteurs (morphismes entr...

  5. Bouger pour la sante - Dr Per Bo Mahler

    CERN Multimedia

    CERN. Geneva

    2012-01-01

    Le mouvement est un facteur fondamental dans l’évolution de l’être humain : il répond grandement à ses besoins fondamentaux. Or, la littérature scientifique ne s’est intéressée réellement à l’activité physique (AP) que dans les années 1990. La journée mondiale de la santé en 2002 a passablement contribué à la reconnaissance de l’AP en tant que déterminant de la santé, dans les pays industrialisés tout comme dans les pays en développement. La littérature est unanime sur les bienfaits de l’AP modérée. Il est admis aujourd’hui que la sédentarité est un facteur de risque égal ou supérieur au tabagisme. Les recommandations : une heure d’activité physique modérée par jour pour les enfants et au moins 150 minutes d’activité modérée ou 75 minutes d’activité vigoureuse par semaine pour les adultes. Malgré cela, une grande proportion de la population reste insuffisamment active. On observe des différences conséquentes selon l’âge, le ...

  6. Soudage des aciers pour application mécanique

    CERN Document Server

    Deveaux, Dominique

    2016-01-01

    Ce guide détermine les bonnes pratiques pour comprendre les risques d’une forme d’assemblage multimatériaux : celui par soudage de nuances à forte teneur en carbone avec des éléments en acier de construction. Dans un premier temps, le rapport passe en revue l’examen des avaries sur des assemblages soudés pour l’application mécanique mettant en cause les aciers. Fissuration par fatigue, rupture fragile, rupture ductile, fissuration à chaud ou à froid sont autant de causes qui seront analysées. Dans un deuxième temps, il se concentre sur la conception des joints soudés. Du choix des nuances à la tenue vis-à-vis de la rupture fragile en passant par l’analyse en fatigue des assemblages soudés, c’est l’ensemble de la problématique qui est pris en compte.

  7. Synthesis copolymer use to reduce pour point temperature of diamond crude oil

    Science.gov (United States)

    Than, Dao Viet; Chuong, Thai Hong; Tuy, Dao Quoc

    2017-09-01

    Diamond oil field is located in Block 01&02 Offshore Vietnam. Crude oil from Diamond Well Head Platform (WHP) is evacuated to FPSO via 20km 10" subsea flexible pipeline. The lowest seabed temperature in the field is 22°C, while the pour point temperature (PPT) of Diamond crude oil is very high (36°C) due to high paraffin content (25%). So studying to research a suitable Pour Point Depressant (PPD) for the crude oil is very important. The PPD must have ability to reduce pour point temperature of crude oil from 36°C to 21°C.

  8. LES JUGES FRANÇAIS ET LA GESTATION POUR AUTRUI

    OpenAIRE

    Gross , Martine; Brunet , Laurence; Giroux , Michelle

    2018-01-01

    International audience; A la différence du Canada où la gestation pour autrui (GPA) est légale, y compris au Québec même si dans cette province, le contrat de GPA est nul et ne peut avoir de valeur exécutoire (Art. 541 C.c.Q. ; Loi sur la procréation assistée 2004, art. 6 ; Giroux 2011 ; Moore 2013) 1 , en France, le recours à la GPA est strictement prohibé. Malgré cela, des couples hétérosexuels et des couples gays, ont recours à la GPA en se rendant dans les pays où elle est légale. Lorsqu'...

  9. QUEL AVENIR POUR LA FINANCE ISLAMIQUE EN TUNISIE ?

    OpenAIRE

    AJILI, WISSEM; GARA, ZEINEB BEN

    2013-01-01

    RESUME: L’article a pour objectif de déterminer les facteurs explicatifs de la réticence (ou non) des tunisiens vis-à-visde la finance islamique et d’apprécier le potentiel de développement d’un système financier islamique en Tunisie sur le moyen-long terme. Ainsi, sur la base d’une étude exploratoire menée conjointement auprès des professionnels de la finance conventionnelle et islamique et des ménages, plusieurs facteurs de réticence ont été identifiés. Néanmoins, tandis que les professionn...

  10. Passeport pour les deux infinis: an educational project in French

    Science.gov (United States)

    Arnaud, Nicolas; Descotes-Genon, Sébastien; Kerhoas-Cavata, Sophie; Paul, Jacques; Robert-Esil, Jean-Luc; Royole-Degieux, Perrine

    2016-04-01

    Passeport pour les deux infinis (;Passport for the two infinities;, in short Pass2i) is a French educational project aiming at promoting the physics of the infinitely small (particle physics) and of the infinitely big (cosmology & astrophysics) to high-school teachers and students. It is managed since 2009 by a small team of outreach experts (physicists and engineers) from the CNRS and the CEA. The Pass2i cornerstone is a reversible book - where each side explores one of the two infinities - and which is given for free to science high school teachers who request it, thanks to the support of French funding agencies. The Pass2i non-profit association wants to be a bridge between science and education: training sessions are organized for teachers, educational resources created and made available for download on the Pass2i website (http://www.passeport2i.fr).

  11. Soft drink "pouring rights": marketing empty calories to children.

    Science.gov (United States)

    Nestle, M

    2000-01-01

    Healthy People 2010 objectives call for meals and snacks served in schools to contribute to overall diets that meet federal dietary guidelines. Sales in schools of foods and drinks high in calories and low in nutrients undermine this health objective, as well as participation in the more nutritious, federally sponsored, school lunch programs. Competitive foods also undermine nutrition information taught in the classroom. Lucrative contracts between school districts and soft drink companies for exclusive rights to sell one brand are the latest development in the increasing commercialization of school food. These contracts, intended to elicit brand loyalty among young children who have a lifetime of purchases ahead of them, are especially questionable because they place schools in the position of "pushing" soft drink consumption. "Pouring rights" contracts deserve attention from public health professionals concerned about the nutritional quality of children's diets.

  12. Caracterisation thermique de modules de refroidissement pour la photovoltaique concentree

    Science.gov (United States)

    Collin, Louis-Michel

    Pour rentabiliser la technologie des cellules solaires, une reduction du cout d'exploitation et de fabrication est necessaire. L'utilisation de materiaux photovoltaiques a un impact appreciable sur le prix final par quantite d'energie produite. Une technologie en developpement consiste a concentrer la lumiere sur les cellules solaires afin de reduire cette quantite de materiaux. Or, concentrer la lumiere augmente la temperature de la cellule et diminue ainsi son efficacite. Il faut donc assurer a la cellule un refroidissement efficace. La charge thermique a evacuer de la cellule passe au travers du recepteur, soit la composante soutenant physiquement la cellule. Le recepteur transmet le flux thermique de la cellule a un systeme de refroidissement. L'ensemble recepteur-systeme de refroidissement se nomme module de refroidissement. Habituellement, la surface du recepteur est plus grande que celle de la cellule. La chaleur se propage donc lateralement dans le recepteur au fur et a mesure qu'elle traverse le recepteur. Une telle propagation de la chaleur fournit une plus grande surface effective, reduisant la resistance thermique apparente des interfaces thermiques et du systeme de refroidissement en aval vers le module de refroidissement. Actuellement, aucune installation ni methode ne semble exister afin de caracteriser les performances thermiques des recepteurs. Ce projet traite d'une nouvelle technique de caracterisation pour definir la diffusion thermique du recepteur a l'interieur d'un module de refroidissement. Des indices de performance sont issus de resistances thermiques mesurees experimentalement sur les modules. Une plateforme de caracterisation est realisee afin de mesurer experimentalement les criteres de performance. Cette plateforme injecte un flux thermique controle sur une zone localisee de la surface superieure du recepteur. L'injection de chaleur remplace le flux thermique normalement fourni par la cellule. Un systeme de refroidissement est installe

  13. Changer la pensée pour changer le monde.

    Directory of Open Access Journals (Sweden)

    Arnaud Esquerre

    2008-12-01

    Full Text Available « Toute volonté de changement comporte donc des risques ; mais la question est de savoir si ces risques ne sont pas moins grands que ceux qui résulteraient du refus du changement ». Cette phrase, qui pourrait être employée par des politiques au pouvoir pour justifier leur volonté de mener des réformes, et mêmes des ruptures, dans les années 2000, date pourtant des années 1970. Extraite d’un texte de Pierre Aubenque, « Philosophie et changement » 1 , elle est au cœur ...

  14. Avaliação económica do erlotinib, docetaxel, pemetrexedo e tratamento de suporte no tratamento de segunda ou terceira linhas de doentes com cancro do pulmão de não pequenas células

    Directory of Open Access Journals (Sweden)

    A. Araújo

    2008-11-01

    Full Text Available Resumo: Objectivo: Avaliar o custo-efectividade de erlotinib na segunda ou terceira linha do tratamento do cancro do pulmão de não pequenas células (CPNPC avançado ou metastizado versus docetaxel, pemetrexedo ou tratamento de suporte.Material e métodos: Análises de minimização de custos e custo-utilidade. Horizonte temporal: dois anos. Perspectiva do Sistema Nacional de Saúde (SNS português. Sobrevivência e tempo até progressão obtidos a partir de três ensaios clínicos. Análise-base inclui doentes com CPNPC avançado ou metastizado em segunda ou terceira linhas. Anos de vida ajustados pela qualidade (ou QALY obtidos a partir de estudo no Reino Unido. Consumo de recursos estimado por painel de peritos portugueses. Incluíram-se apenas custos directos, obtidos a partir de fontes oficiais (preços actualizados para 2008. Taxa de actualização anual: 5%. Análises de sensibilidade: diferentes subpopulações, horizonte temporal a três anos e análise probabilística.Resultados: O custo total/doente foi menor com erlotinib (26 478€ versus docetaxel (29 262€ ou pemetrexedo (32 762€ e superior versus tratamento de suporte (16 112€. Obtiveram-se QALY/doente mais elevados com erlotinib (0,250 versus docetaxel (0,225, pemetrexedo (0,241 ou tratamento de suporte (0,186. Assim, o erlotinib mostrou-se “dominante” em segunda ou terceira linhas versus docetaxel e pemetrexedo. A análise de sensibilidade comprova a robustez dos resultados.Conclusões: A substituição de docetaxel ou pemetrexedo por erlotinib poderia contribuir para uma redução anual dos gastos do SNS que se estima (taxas substituição: 5%-65% com uma variação entre 135 046€-1 755 602€ e entre 291 801€-3 793 409€, respectivamente, e com ganho em termos de QALY.Rev Port Pneumol 2008; XIV (6: 803-827 Abstract: Aim: Evaluate costs and benefits of

  15. Sud du Sahara | Page 100 | CRDI - Centre de recherches pour le ...

    International Development Research Centre (IDRC) Digital Library (Canada)

    information libres pour les services de santé en Afrique. Langue French. Read more about Open Architecture, Standards and Information Systems (OASIS) for Healthcare in Africa. Langue English. Read more about Communication dans le but ...

  16. La Mycorhize a arbuscules : quels benefices pour I'homme et son ...

    African Journals Online (AJOL)

    la production vegetale mais aussi pour une gestion et une remediation des sols degrades respectueuses de la .... phytoremediation des sols pollues. Les ... mecanisme central dans la regulation de ..... Soil Science Society of America Journal,.

  17. Sexospécificités | Page 186 | CRDI - Centre de recherches pour le ...

    International Development Research Centre (IDRC) Digital Library (Canada)

    ... et font connaître des solutions pratiques pour la culture des légumineuses à graines ... Langue French ... Langue French ... Langue French ... Langue French ... A project supported by the Canadian International Food Security Research Fund ...

  18. Analyses de la dégradation du lac Kinkony pour la conservation du ...

    African Journals Online (AJOL)

    Le lac Kinkony fait partie des habitats clefs pour la biodiversité du Complexe des ... provide favoured habitat for numerous endemic and endangered avian, fish ... on fauna is essential for developing regional conservation and natural resource ...

  19. Sexospécificités | Page 224 | CRDI - Centre de recherches pour le ...

    International Development Research Centre (IDRC) Digital Library (Canada)

    Le programme Recherche pour la lutte mondiale contre le tabac (RMCT) du CRDI aide des chercheurs des pays en développement à contrer l'influence des géants de l'industrie du tabac aux ressources financières colossales. Read more about Pour que brûle le feu du changement. Langue French. IDRC 's Research for ...

  20. Recherche pour le développement — Vietnam | CRDI - Centre de ...

    International Development Research Centre (IDRC) Digital Library (Canada)

    11 janv. 2011 ... L'expression Doi Moi (en gros, « reconstruction») a été adoptée en 1986 pour décrire un ensemble de politiques conçues pour favoriser un « socialisme de marché » grâce à d'importantes mesures de libre entreprise, tout en préservant la primauté politique et le pouvoir de gouverner du Parti communiste.

  1. Innovation au sens large. Une étude pour la mesure de l’innovation.

    NARCIS (Netherlands)

    Pauwels, Fernando; Cortese, Valter; Martinez, Esteban; Forrier, Anneleen; Van Hootegem, Geert; Van Ruysseveldt, Joris; Manshoven, Joke; Teirlinck, Peter

    2010-01-01

    L’innovation est considérée en général comme l’un des facteurs les plus importants pour la compétitivité des entreprises et pour la stimulation de la croissance économique et de l’emploi. Il va de soi que la mise en oeuvre d’une politique d’innovation efficiente est basée sur l’identification des

  2. Fonds d'innovation en vaccins pour le bétail : renforcement des ...

    International Development Research Centre (IDRC) Digital Library (Canada)

    Fonds d'innovation en vaccins pour le bétail : renforcement des capacités de recherche. Ce projet donne l'autorisation d'appuyer le renforcement des capacités afin de mettre en place le Fonds d'innovation en matière de vaccins pour le bétail et de le gérer. Le Fonds vise à financer le développement de vaccins de qualité ...

  3. Dé-mondialiser le secteur minier pour développer l'Afrique

    African Journals Online (AJOL)

    Conseil pour le développement de la recherche en sciences sociales en Afrique, 2017 ... des lieux d'extraction des matières premières, tandis que la transformation .... Noirs, en passant par la colonisation pour finir dans cette nouvelle forme ... et la Communauté européenne de l'énergie atomique, l'Afrique se doit aussi ...

  4. Données probantes pour la réduction de la violence urbaine au ...

    International Development Research Centre (IDRC) Digital Library (Canada)

    28 sept. 2016 ... Image. Favela de Prazeres. FLICKR / Dany13. COLLECTION: HISTOIRE À SUCCÈS | VILLES SÛRES ET INCLUSIVES. Quelles stratégies fonctionnent — et ne fonctionnent pas — pour réduire la violence dans les centres urbains ? Pour répondre à cette question, l'initiative Villes sûres et inclusives ...

  5. Une vision planétaire pour les petites entreprises d'Égypte

    International Development Research Centre (IDRC) Digital Library (Canada)

    L'idée : changement à court terme et gain à long terme. On a souvent dit du milieu des affaires égyptien qu'il était extrêmement « inhospitalier ». Pour ... le SMEPol ont analysé le contexte commercial et les politiques en vigueur en Égypte afin d'établir clairement et précisément les mesures requises pour améliorer la ...

  6. Sri Lanka : tous les projets | CRDI - Centre de recherches pour le ...

    International Development Research Centre (IDRC) Digital Library (Canada)

    Exploiter les données massives pour atteindre les objectifs de développement durable - Créer des compétences dans l'hémisphère sud ... Nombre de pays en développement sont dépourvus des capacités et des ressources requises pour recueillir et analyser des données aux fins de ... Sujet: AGRICULTURE, Gender.

  7. La communication participative pour le développement : Un agenda ...

    International Development Research Centre (IDRC) Digital Library (Canada)

    1 janvier 1996. ISBN : Épuisé. 138 pages. e-ISBN : 1552503909. Téléchargez le PDF. Il y a deux ans, le Centre de recherches pour le développement international a créé CIME, un programme de communication pour le développement, afin de témoigner de l'importance des interrelations entre la Communication à la base, ...

  8. Analyses des taxes et de la pauvreté pour faire avancer la lutte ...

    International Development Research Centre (IDRC) Digital Library (Canada)

    Analyses des taxes et de la pauvreté pour faire avancer la lutte contre le tabagisme à l'échelle mondiale. Ce projet, mis en place par l'Instituto Nacional de Salud Pública du Mexique, consiste à entreprendre une série d'études préliminaires pour contribuer aux travaux de la nouvelle commission sur la lutte antitabac à ...

  9. Appel à propositions : Innovations pour l'inclusion économique des ...

    International Development Research Centre (IDRC) Digital Library (Canada)

    20 mars 2018 ... L'Organisation internationale du Travail rapporte que près d'un cinquième des ... organismes de coopération internationale ont pris des mesures pour promouvoir ... de début de carrière pour les femmes scientifiques maintenant offertes ... Droits d'auteur · Éthique de la recherche · Politique de libre accès ...

  10. Ecrire pour quoi faire ? : lettres, comptes rendus, résumés de textes

    CERN Document Server

    Grabner, Cécile

    1981-01-01

    Pour tous ceux, adultes et adolescents, qui veulent vaincre leurs difficultés d'expression écrite dans leur vie quotidienne professionnelle ou scolaire, écrire pour quoi faire ? lettres comptes rendus résumés de textes est un outil de travail à utiliser en formation de groupe ou en formation autonome en fonction du niveau et du rythme personnels.

  11. Évaluation organisationnelle : Cadre pour l'amélioration de la ...

    International Development Research Centre (IDRC) Digital Library (Canada)

    Le présent ouvrage propose une méthodologie simple pour diagnostiquer les forces et les faiblesses institutionnelles lorsque l'on se lance dans des activités de développement. Les bénéficiaires peuvent ainsi satisfaire les gouvernements et les organismes donateurs qui font de plus en plus pression pour que le ...

  12. Résultats de recherche | Page 3 | CRDI - Centre de recherches pour ...

    International Development Research Centre (IDRC) Digital Library (Canada)

    Une plateforme pour la mise au point d'un vaccin anti-adénovirus non réplicatif contre les maladies aviaires. La volaille constitue un élevage essentiel en Afrique subsaharienne, surtout pour la sécurité alimentaire et l'indépendance économique des jeunes et des femmes vivant en milieu rural. Date de publication.

  13. Bourse de recherche pour l'étude du développement de la Birmanie ...

    International Development Research Centre (IDRC) Digital Library (Canada)

    Bourse de recherche pour l'étude du développement de la Birmanie. Les changements récents qui se sont produits en Birmanie offrent un climat favorable pour entreprendre des recherches sur le développement durable fondées sur des données probantes, ce dont on a besoin de toute urgence. Cette subvention servira à ...

  14. Jeter de nouvelles bases pour le bien de la jeunesse dans les pays ...

    International Development Research Centre (IDRC) Digital Library (Canada)

    16 mars 2015 ... Le CRDI dote les établissements locaux de moyens pour qu'ils puissent aider les pays de la région à répondre aux attentes grandissantes de leurs jeunes citoyens. Afin de mieux comprendre dans quelle mesure les bouleversements en Tunisie et en Égypte ont modifié la donne pour les entrepreneurs, ...

  15. Exploitation du savoir autochtone afin de créer des emplois pour les ...

    International Development Research Centre (IDRC) Digital Library (Canada)

    Transformer l'emploi des femmes. L'étude explorera le potentiel d'approches novatrices locales ou autochtones visant à appuyer l'emploi en milieu rural. Les chercheurs auront recours à des méthodes quantitatives et qualitatives pour analyser la façon dont le savoir autochtone et la technologie peuvent être utilisés pour ...

  16. : tous les projets | Page 532 | CRDI - Centre de recherches pour le ...

    International Development Research Centre (IDRC) Digital Library (Canada)

    La corruption représente un défi de taille pour la démocratie s'agissant de la surveillance de l'utilisation qui est faite des deniers publics, et pour le développement en général. Date de début : 26 octobre 2006. End Date: 26 octobre 2009. Sujet: RESEARCH FELLOWSHIPS, CORRUPTION, Governance. Région: Kenya ...

  17. Ressources minières en Afrique : Quelle réglementation pour le ...

    International Development Research Centre (IDRC) Digital Library (Canada)

    Ressources minières en Afrique : Quelle réglementation pour le développement ? Couverture du livre Ressources minières en Afrique : Quelle réglementation pour le développement ? Directeur(s):. Bonnie Campbell. Maison(s) d'édition: Presses de l'Université du Québec, CRDI. 6 juillet 2009. ISBN : 9782760525214.

  18. Résultats de recherche | Page 9 | CRDI - Centre de recherches pour ...

    International Development Research Centre (IDRC) Digital Library (Canada)

    Depuis longtemps, l'Ouganda fait face à des pressions sociales qui ont parfois donné lieu à des épisodes de violence, tels que des insurrections, des conflits armés et des activités criminelles, pour n'en nommer que quelques-uns. Projet. Développer une expertise en société civile pour susciter une gouvernance ...

  19. Capacités en science du comportement pour relever les facteurs qui ...

    International Development Research Centre (IDRC) Digital Library (Canada)

    Pour combler cette importante lacune, ce projet financera les études de maîtrise d'un étudiant nigérian en psychologie à l'Université d'Ottawa. Cette formation aidera à concevoir des outils et des stratégies pour cerner les principaux obstacles et facteurs de motivation psychosociaux relatifs à la participation et à la rétention ...

  20. : tous les projets | Page 37 | CRDI - Centre de recherches pour le ...

    International Development Research Centre (IDRC) Digital Library (Canada)

    Sujet: MOTIVATION. Région: Argentina, Brazil, Chile, Colombia, Mexico, Peru, Uruguay. Programme: Employment and Growth. Financement total : CA$ 858,000.00. Accroître les possibilités pour les jeunes vulnérables : entendre leur voix pour éclairer les politiques. Projet. Ce projet s'attaquera au défi du chômage chez les ...

  1. Air Intakes for High Speed Vehicles (Prises d’Air pour Vehicules a Grande Vitesse)

    Science.gov (United States)

    1991-09-01

    d’essai disponibles . Les r6su!tais des cas d’cssais peuvent servir pour des comparaisons ultlrieures et doivent ýtrc considtrds comme un premier pas pour...MtR3sURL.,1tNl IfflifiOm ROW i;IG. 3.6.2; SrRT1 WARLL PRESSURES AROUND ’,OHL 1. [P TESI CASE .3 2 TOP AND BO[TOfl ROW (DORNIER) AM~ c C; --’ ------ ±-.-1

  2. Nouvelles et activités | Page 4 | CRDI - Centre de recherches pour le ...

    International Development Research Centre (IDRC) Digital Library (Canada)

    Recherche pour un monde climato-intelligent. Lors d'une série de conférences présentées dans le cadre de déjeuners parlementaires, le Centre de recherches pour le développement international (CRDI) présentera les résultats atteints grâce au financement d'adaptation et de développement. Bulletin du CRDI — février ...

  3. Ce que nous faisons | Page 42 | CRDI - Centre de recherches pour ...

    International Development Research Centre (IDRC) Digital Library (Canada)

    Agriculture en terrasses au Népal et trousses d'agriculture durable (FCRSAI 2e phase). Ce projet mettra à l'essai diverses innovations en matière d'agriculture en terrasses et offrira des stratégies aux ONG pour aider 100 000 entrepreneurs népalais en créant une nouvelle entreprise pour appuyer les ventes de produits.

  4. Pour mieux profiter des avantages commerciaux : le Réseau latino ...

    International Development Research Centre (IDRC) Digital Library (Canada)

    2011-07-13

    Pour mieux profiter des avantages commerciaux : le Réseau latino-américain sur le commerce. July 13, 2011. Image. Kevin Conway. Éloigner les menaces et maximiser les possibilités : voilà le mantra des négociateurs commerciaux de par le monde. Pour que la stratégie réussisse, toutefois, les négociateurs et leurs ...

  5. Résultats de recherche | Page 4 | CRDI - Centre de recherches pour ...

    International Development Research Centre (IDRC) Digital Library (Canada)

    Depuis longtemps, l'Ouganda fait face à des pressions sociales qui ont parfois donné lieu à des épisodes de violence, tels que des insurrections, des conflits armés et des activités criminelles, pour n'en nommer que quelques-uns. Projet. Développer une expertise en société civile pour susciter une gouvernance ...

  6. Foire aux questions — AIPRP | CRDI - Centre de recherches pour le ...

    International Development Research Centre (IDRC) Digital Library (Canada)

    Centre de recherches pour le développement international. CP 8500 150, rue Kent Ottawa (Ontario) K1G 3H9. Nota. Des frais de 5 $ payables au Centre de recherches pour le développement international sont exigés avant que le traitement de votre demande en vertu de la Loi sur l'accès à l'information puisse commencer.

  7. Des solutions novatrices pour accroître la sécurité alimentaire de ...

    International Development Research Centre (IDRC) Digital Library (Canada)

    Corey Piccioni

    Canada par l'entremise d'Affaires étrangères, Commerce et Développement Canada, est un programme du Centre de recherches pour le développement international, organisme canadien. Centre de recherches pour le développement international. 150, rue Kent * CP 8500 * Ottawa ON Canada K1G 3H9 * Tél.: +1 613 ...

  8. : tous les projets | Page 375 | CRDI - Centre de recherches pour le ...

    International Development Research Centre (IDRC) Digital Library (Canada)

    L'amélioration de la couverture vaccinale s'inscrit dans le quatrième objectif du Millénaire pour le développement; il s'agit là d'une étape essentielle pour la réduction du taux de mortalité infantile. Date de début : 2 mars 2009. End Date: 31 décembre 2013. Sujet: RESEARCH FELLOWSHIPS, OPERATIONS RESEARCH, ...

  9. Asie | CRDI - Centre de recherches pour le développement ...

    International Development Research Centre (IDRC) Digital Library (Canada)

    ... défis agricoles, environnementaux, technologiques, sociaux et économiques de l'Asie. Grâce à nos investissements stratégiques, nous aidons les acteurs régionaux à participer plus efficacement à résolution des problèmes régionaux. Qu'en résulte-t-il ? Des dirigeants régionaux forts, pour aujourd'hui et pour demain.

  10. Possessive pour in the French Lexicon of the Ivory Coast and Language Contact

    Directory of Open Access Journals (Sweden)

    Akissi Boutin, Béatrice

    2007-01-01

    Full Text Available Any variationist study of Ivory Coast French needs to take into account sociolinguistic considerations and systemic features of other contact languages. For instance, there is a specific usage of pour against which the interference hypothesis can easily be tested:FI: Le kaki que je porte présentement, c'est pour un bachelier qui me l'a laissé avant de partir en fac, cadeau. (Lafage 2003: 676. Avant de te moquer du linge de ta voisine, regarde si pour toi est propre..In Ivory Coast French, pour (N/Pro can display a variety of functions: it can be part of associative predications, it can stand for genitive phrases in an anaphoric construction, make reference to an object in relation with another and participate in various idiomatic expressions.This paper has a twofold objective. First, I argue that pour (N/Pro constructions has to be analysed as an empty headed "associative" noun phrase. Second, I will show the relevance of extra- AND intersystemic factors in accounting for language variation. Incidentally, the use of pour (N/Pro constructions seems to be conditioned by the availability of similar constructions in other Ivory Coast languages on the one hand, such as baoule (o liε or dioula (à tá, and, cultural needs on the other.

  11. Fabrication de transistors monoelectroniques pour la detection de charge

    Science.gov (United States)

    Richard, Jean-Philippe

    Le transistor monoelectro'nique (SET) est un candidat que l'on croyait avoir la capacite de remplacer le transistor des circuits integres actuel (MOSFET). Pour des raisons de faible gain en voltage, d'impedance de sortie elevee et de sensibilite aux fluctuations de charges, il est considere aujourd'hui qu'un hybride tirant profit des deux technologies est plus avantageux. En exploitant sa lacune d'etre sensible aux variations de charge, le SET est davantage utilise dans des applications ou la detection de charge s'avere indispensable, notamment dans les domaines de la bio-detection et de l'informatique quantique. Ce memoire presente une etude du transistor monoelectronique utilise en tant que detecteur de charge. La methode de fabrication est basee sur le procede nanodamascene developpe par Dubuc et al. [11] permettant au transistor monoelectronique de fonctionner a temperature ambiante. La temperature d'operation etant intimement liee a la geometrie du SET, la cle du procede nanodamascene reside dans le polissage chimico-mecanique (CMP) permettant de reduire l'epaisseur des SET jusqu'a des valeurs de quelques nanametres. Dans ce projet de maitrise, nous avons cependant opte pour que le SET soit opere a temperature cryogenique. Une faible temperature d'operation permet le relachement des contraintes de dimensions des dispositifs. En considerant les variations de procedes normales pouvant survenir lors de la fabrication, la temperature d'operation maximale calculee en conception s'etend de 27 K a 90 K, soit une energie de charge de 78 meV a 23 meV. Le gain du detecteur de charge etant dependant de la distance de couplage, les resultats de simulations demontrent que cette distance doit etre de 200 nm pour que la detection de charge soit optimale. Les designs concus sont ensuite fabriques sur substrat d'oxyde de silicium. Les resultats de fabrication de SET temoignent de la robustesse du procede nanodamascene. En effet, les dimensions atteintes experimentalement s

  12. Bourses Écosystèmes et santé humaine pour les cycles supérieurs ...

    International Development Research Centre (IDRC) Digital Library (Canada)

    Le montant de chaque bourse sera de 15 000 CAD pour la recherche sur le terrain et jusqu'à 4 000 CAD pour participer à une conférence afin de diffuser les résultats des recherches ou pour retourner sur le terrain afin de présenter ses constatations aux parties prenantes locales. En outre, les boursiers participeront à une ...

  13. Informations pour les retraités - French version only

    CERN Multimedia

    Ph. Bernard

    2004-01-01

    Chers Collègues, Vous avez été nombreux à accepter l'invitation du Directeur général pour notre matinée du 15 octobre. Nous sommes très heureux de pouvoir accueillir tous ceux qui ont répondu à cette invitation. La réunion se tiendra dans l'Amphitéâtre principal et sera transmise par télévision dans la Salle du Conseil et dans les 4 salles de réunion du bât. 40 (40-S2-A01, 40-S2-B01, 40-S2-C01, 40-S2-D01). Elle commencera à 9 heures précises et nous vous prions de venir bien avant afin que tous puissent trouver leurs places dans les différentes salles. Nous répéterons cette information dans les prochains Bulletins et vous donnerons de plus amples détails si possible. Ph. Bernard Président, Comité du GAC

  14. Système de guidage pour ponts roulants

    CERN Document Server

    Caldérone, A

    1999-01-01

    L'équipe de maintenance des ponts roulants ST-HM-PR est souvent confrontée à résoudre des problèmes d'usure de galets de translation. Ces défauts apparaissent particulièrement lorsque l'on travaille avec des charges décentrées et sur des ponts roulants de grande portée. Pour remédier à ces défauts, plutôt que d'utiliser une solution mécanique conventionnelle, le groupe HM a développé un système électronique qui consiste à mesurer la distance entre le rail de roulement et les joues des roues, traiter ce signal et corriger la vitesse des moteurs respectifs de translation, de façon à maintenir le pont roulant centré. Ce système a été entièrement réalisé au sein du groupe HM et installé sur deux ponts roulants équipant le hall EHN1.

  15. Le Web pour enseigner par projets et favoriser la collaboration

    Directory of Open Access Journals (Sweden)

    Sylvie Ratté

    2004-01-01

    Full Text Available L’utilisation du Web présentée dans cet article vient appuyer une démarche pédagogique fondée sur le partage des savoirs. Dans le contexte d’une simulation industrielle, les étudiants d’un cours de programmation avancée doivent apprendre à partager leur expertise, à communiquer clairement leurs questions, à décrire des problèmes et à faire face à des retournements inattendus. Le Web devient un espace de collaboration pour diffuser les requêtes d’un client fictif, les directives, les travaux préliminaires et les ententes. Les résultats obtenus tendent à suggérer que cette approche globale force l’étudiant à mieux planifier, l’invite à mieux formuler et décrire les problèmes, augmente le niveau de collaboration et facilite la production d’analogies. Un système facilitant la logistique entourant la revue par les pairs (récupération des travaux, construction d’une grille d’évaluation et diffusion des résultats est également présenté.

  16. Multi-institutional phase I study of low-dose ultra-fractionated radiotherapy as a chemosensitizer for gemcitabine and erlotinib in patients with locally advanced or limited metastatic pancreatic cancer

    International Nuclear Information System (INIS)

    Konski, Andre; Meyer, Joshua E.; Joiner, Michael; Hall, Michael J.; Philip, Philip; Shields, Anthony; McSpadden, Erin; Choi, Minsig; Adaire, Beth; Duncan, Gail; Meropol, Neal J.; Cescon, Terrence P.; Cohen, Steven J.

    2014-01-01

    Purpose: Gemcitabine (G) has been shown to sensitize pancreatic cancer to radiotherapy but requires lower doses of G and thus delays aggressive systemic treatment, potentially leading to distant failure. We initiated a phase I trial combining ultra-fractionated low-dose radiotherapy with full dose G and erlotinib in the treatment of patients with advanced pancreatic cancer. Methods: Patients with locally advanced or metastatic pancreatic cancer confined to the abdomen and an ECOG performance status (PS) of 0–1 who had received 0–1 prior regimens (without G or E) and no prior radiotherapy were eligible. Patients were treated in 21 day cycles with G IV days 1 and 8, E once PO QD, and twice daily RT fractions separated by at least 4 h on days 1, 2, 8, and 9. Whole abdominal RT fields were used. Primary endpoint was to define dose limiting toxicity (DLT) and the maximum tolerated dose (MTD). Results: 27 patients (median age 64 years and 15 male) were enrolled between 11/24/08 and 4/12/12. 1 patient withdrew consent prior to receiving any protocol therapy. 17 patients had a PS of 1. The majority of patients were stage IV. One DLT was noted out of 7 patients at dose level (DL) 1. Subsequently no DLTs were noted in 3 patients each enrolled at DL2-4 or 11 patients in the expansion cohort. The majority of grade 3 toxicities were hematologic with 1 grade 5 bowel perforation in dose level 1 in cycle 4. Best response in 24 evaluable patients: PR (8), stable (15), PD 1. Median survival for the entire group was 9.1 months. Conclusion: This phase I study combining low-dose ultra-fractionated RT as a sensitizer to full dose G plus E was well tolerated with encouraging efficacy. This represents a novel strategy worthy of further investigation in advanced pancreatic cancer patients

  17. Innovations en vaccinologie: enjeux et perspectives pour l’Afrique

    Science.gov (United States)

    Diop, Doudou; Sanicas, Melvin

    2017-01-01

    La vaccination est incontestablement l’une des interventions de santé publique les plus efficaces et les plus rentables qui soient. Les vaccins continuent de révolutionner notre capacité à prévenir les maladies et à améliorer la santé. Avec toutes les avancées technologiques, nous sommes en mesure d’étendre les avantages des vaccins à plus de gens et de fournir une meilleure protection contre les maladies infectieuses mortelles. Toutefois, avec le développement incessant de nouvelles souches microbiennes à travers le monde, la recherche en vaccinologie se doit d’innover continuellement. D’énormes progrès ont été réalisés pour améliorer la couverture vaccinale et introduire de nouveaux vaccins en Afrique. De nouveaux types de vaccins associés à des outils de vectorisation, d’administration et de délivrance spécifiques mais aussi des adjuvants susceptibles de moduler finement la réponse immunitaire sont attendus dans le futur. En Afrique, il est nécessaire de développer une approche régionale afin de répondre efficacement aux nombreux défis. Une meilleure information, la formation des personnels de santé en vaccinologie et des recherches bien ciblées sont les clés des futurs accomplissements dans le domaine. PMID:28690749

  18. Modèle exploitable pour la définition de la commande du robot

    OpenAIRE

    ZIMMER-CHEVRET, Sandra; LANGLOIS, Laurent; BEN ATTAR, Amarilys

    2014-01-01

    Ce document traite de la modélisation des actions mécaniques entre l’outil et la matière. L’objectif est de définir un modèle exploitable pour la définition de la commande du robot. Dans un premier temps, le rapport présente une synthèse bibliographique des modèles des interactions mécaniques développés à ce jour. Pour un modèle choisi, les paramètres constituant ce dernier ont été calculés à partir de données expérimentales. Puis, la validité du modèle a été étudiée. Pour une même configurat...

  19. Etude du secteur des préparations pour desserts 2009

    OpenAIRE

    Combris, Pierre; Goglia, Raffaella; Henini, Marion; Lafitte, Caroline; Soler, Louis Georges; Spiteri, Marine; Stevenin, Florence; Observatoire de la Qualité de l'Alimentation

    2010-01-01

    Cette étude sectorielle de suivi du marché des préparations pour desserts repose principalement sur les informations relevées sur les emballages, notamment les valeurs nutritionnelles, la taille des portions indiquées, les repères nutritionnels, les recommandations de consommation… Pour cette première année d’étude, la base de données compte 155 références, correspondant à une couverture d’au moins 67% du marché en volume. Pour affiner au mieux les traitements effectués, le secteur a été déco...

  20. La renaissance du temps pour en finir avec la crise de la physique

    CERN Document Server

    Smolin, Lee

    2014-01-01

    La question du Temps est au coeur de toutes les problématiques scientifiques, de la cosmologie à la mécanique quantique. L’un des plus grands physiciens d’aujourd’hui, Lee Smolin, expose sa conception du Temps et ses implications sur la perception de notre environnement. Le Temps est-il une illusion qui cache une vérité éternelle, ou une réalité physique de notre Univers ? Lee Smolin opte pour la réalité du Temps, s’opposant en cela à la majorité des penseurs, physiciens ou philosophes, inspirés pour les uns par la théorie de la Relativité d’Einstein et pour les autres par les idées platoniciennes.

  1. Europe CERN recherche - Pret de 300 millions d'euros de la BEI pour l'accelerateur de particules

    CERN Multimedia

    2002-01-01

    "La Banque europeenne d'investissement (BEI) va preter 300 millions d'euros pour financer la phase finale de la construction du grand accelerateur de particules LHC (Large Hadron Collider) du CERN, a indique jeudi l'organisation europeenne pour la recherche nucleaire" (1/2 page).

  2. La Mycorhize à arbuscules : quels bénéfices pour l'homme et son ...

    African Journals Online (AJOL)

    La Mycorhize à arbuscules : quels bénéfices pour l'homme et son ... et quantitative de la production végétale mais aussi pour une gestion et une remédiation ... Mycorrhizal symbiosis, and specifically arbuscular mycorrhization, which occurs ...

  3. Partenariats pour le développement de la capacité en matière de ...

    International Development Research Centre (IDRC) Digital Library (Canada)

    12 janv. 2011 ... Joanna Chataway, James Smith et David Wield. Ce document a pour dessein de conforter les efforts canadiens et britanniques en examinant sept approches différentes en Afrique et en offrant des suggestions pour faire progresser cette action. L'élaboration de programmes probants et voués au succès ...

  4. Compétences pour les PME de l'Amérique centrale dans l'économie ...

    International Development Research Centre (IDRC) Digital Library (Canada)

    ... compétences nécessaires; b) des recherches pour comprendre les modèles sociaux ... Il existe un lien bien documenté entre les compétences nécessaires pour ... Bien que ces compétences ne soient pas nécessairement axées sur les TIC, ...

  5. Nouvel outil d'évaluation pour apprécier la qualité de la recherche ...

    International Development Research Centre (IDRC) Digital Library (Canada)

    25 avr. 2016 ... Cette évaluation, qui comporte trois phases, a pour but de définir et de ... Pour ce faire, on a analysé des outils et des démarches d'évaluation de l'excellence ... The Research Quality Plus (RQ+) Assessment Instrument (texte ...

  6. Les Fintech sont-elles une opportunité ou une menace pour les banques traditionnelles ?

    OpenAIRE

    Blanc, Aldwin; Sonney, Frédéric

    2018-01-01

    Dans ce travail, nous étudierons les potentielles opportunités et menaces que sont les Fintech pour les institutions bancaires. Cela nous permettra de savoir si, à l’avenir, ces entreprises vont s’imposer et remplacer les banques telles que nous les connaissons ou alors aider, forcer les acteurs traditionnels à effectuer leur révolution numérique pour répondre aux nouvelles attentes des clients. Afin de répondre à cette interrogation, les trois strates de l’environnement bancaire ont été anal...

  7. LE RISQUE DE LIQUIDITE POUR UNE BANQUE ISLAMIQUE : ENJEUX ET GESTION

    OpenAIRE

    KHOUTEM, BEN JEDIDIA; MOULDI, JLASSI

    2013-01-01

    La liquidité est une question cruciale pour les banques islamiques. L’enjeu de la liquidité et sa gestion présentent des défis pour ces banques. D’abord, les banques islamiques sont exposées au risque de liquidité3 dans un contexte de faiblesses structurelles du système financier qui pèsent sur leur solvabilité et leur liquidité (Sundararajan and Errico, 2002 ; Salman, 2004 ; El-Hawary et al, 2007 ; Akkizidis et Khandelwal, 2008, Al-Muharrami et Hardy, 2013). En fait, la plupart des banques i...

  8. À la recherche de mesures pour faire en sorte que les petits pays d ...

    International Development Research Centre (IDRC) Digital Library (Canada)

    Cette subvention aidera les petits pays d'Asie du Sud à se doter de politiques en matière de biotechnologie et à s'appuyer sur cette dernière pour remédier à des priorités immédiates et fondamentales en matière de développement. Pour ce faire, elle appuiera deux activités distinctes, mais interreliées. La première est une ...

  9. Analysis Of DWPF Sludge Batch 7A (Macrobatch 8) Pour Stream Samples

    International Nuclear Information System (INIS)

    Johnson, F.

    2012-01-01

    The Defense Waste Processing Facility (DWPF) began processing Sludge Batch 7a (SB7a), also referred to as Macrobatch 8 (MB8), in June 2011. SB7a is a blend of the heel of Tank 40 from Sludge Batch 6 (SB6) and the SB7a material that was transferred to Tank 40 from Tank 51. SB7a was processed using Frit 418. During processing of each sludge batch, the DWPF is required to take at least one glass sample to meet the objectives of the Glass Product Control Program (GPCP), which is governed by the DWPF Waste Compliance Plan, and to complete the necessary Production Records so that the final glass product may be disposed of at a Federal Repository. Three pour stream glass samples and two Melter Feed Tank (MFT) slurry samples were collected while processing SB7a. These additional samples were taken during SB7a to understand the impact of antifoam and the melter bubblers on glass redox chemistry. The samples were transferred to the Savannah River National Laboratory (SRNL) where they were analyzed. The following conclusions were drawn from the analytical results provided in this report: (1) The sum of oxides for the official SB7a pour stream glass is within the Product Composition Control System (PCCS) limits (95-105 wt%). (2) The average calculated Waste Dilution Factor (WDF) for SB7a is 2.3. In general, the measured radionuclide content of the official SB7a pour stream glass is in good agreement with the calculated values from the Tank 40 dried sludge results from the SB7a Waste Acceptance Program Specification (WAPS) sample. (3) As in previous pour stream samples, ruthenium and rhodium inclusions were detected by Scanning Electron Microscopy-Electron Dispersive Spectroscopy (SEM-EDS) in the official SB7a pour stream sample. (4) The Product Consistency Test (PCT) results indicate that the official SB7a pour stream glass meets the waste acceptance criteria for durability with a normalized boron release of 0.64 g/L, which is an order of magnitude less than the Environmental

  10. Penser les métropoles pour les « individus » ?

    Directory of Open Access Journals (Sweden)

    Marc Dumont

    2006-03-01

    Full Text Available Les instruments dont on dispose aujourd’hui pour décrire et expliquer les réalités métropolitaines contemporaines ne sont pas entièrement satisfaisants : ils ne permettent pas toujours d’identifier les vraies questions qui se présentent à ceux qui produisent la ville. Partant de ce constat, le sociologue Alain Bourdin synthétise dans son nouvel essai des réflexions issues de sa pratique de recherche et de dialogue avec le monde des institutions, pour y proposer une lecture de la ...

  11. Maroc | CRDI - Centre de recherches pour le développement ...

    International Development Research Centre (IDRC) Digital Library (Canada)

    Appliquer à grande échelle la chaîne de valeur du quinoa pour améliorer la sécurité alimentaire dans les communautés pauvres/rurales du Maroc. Au Maroc, la pauvreté rurale demeure un problème et l'on s'attend à ce qu'il s'accentue. Voir davantageAppliquer à grande échelle la chaîne de valeur du quinoa pour ...

  12. STUDI PERBANDINGAN PERFORMANCE ALGORITMA HEURISTIK POUR TERHADAP MIXED INTEGER PROGRAMMING DALAM MENYELESAIKAN PENJADWALAN FLOWSHOP

    Directory of Open Access Journals (Sweden)

    Tessa Vanina Soetanto

    2004-01-01

    Full Text Available This paper presents a study about new heuristic algorithm performance compared to Mixed Integer Programming (MIP method in solving flowshop scheduling problem to reach minimum makespan. Performance appraisal is based on Efficiency Index (EI, Relative Error (RE and Elapsed Runtime. Abstract in Bahasa Indonesia : Makalah ini menyajikan penelitian tentang performance algoritma heuristik Pour terhadap metode Mixed Integer Programming (MIP dalam menyelesaikan masalah penjadwalan flowshop dengan tujuan meminimalkan makespan. Penilaian performance dilakukan berdasarkan nilai Efficiency Index (EI, Relative Error (RE dan Elapsed Runtime. Kata kunci: flowshop, makespan, algoritma heuristik Pour, Mixed Integer Programming.

  13. Community Cleaning Services : une alliance hybride pour l'assainissement urbain

    OpenAIRE

    Thieme, Tatiana; DeKoszmovszky, Justin

    2012-01-01

    Cet article vise à analyser les trois phases de développement de l’initiative Community Cleaning Service, soutenu par SC Johnson dans les bidonvilles de Nairorib. Après le lancement du BoP Protocol, puis le développement d’un système de micro-franchise, CCS est devenue une entreprise sociale à but non lucratif. On observe dans ces trois phases les relations complexes qui se tissent, ausi bien pour l’entreprise que pour les micro-franchisés, entre aide et marché.

  14. Community Cleaning Services : une alliance hybride pour l'assainissement urbain

    Directory of Open Access Journals (Sweden)

    Tatiana Thieme

    2012-01-01

    Full Text Available Cet article vise à analyser les trois phases de développement de l’initiative Community Cleaning Service, soutenu par SC Johnson dans les bidonvilles de Nairorib. Après le lancement du BoP Protocol, puis le développement d’un système de micro-franchise, CCS est devenue une entreprise sociale à but non lucratif. On observe dans ces trois phases les relations complexes qui se tissent, ausi bien pour l’entreprise que pour les micro-franchisés, entre aide et marché.

  15. Raisonnement analogique pour la recommandation : premières expérimentations

    OpenAIRE

    Hug, Nicolas; Prade, Henri; Richard, Gilles

    2015-01-01

    Les systèmes de recommandation ont pour vocation de fournir des suggestions intéressantes à leurs utilisateurs. On distingue deux principaux types d'approche pour construire un système de recommandation : les méthodes dites "content-based" et les méthodes dites collaboratives. Encouragés par les bons résultats obtenus par les techniques de classification basées sur les proportions analogiques, nous nous intéressons ici à la conception de techniques de recommandation elles aussi basées sur les...

  16. Flavoring culture / Le goût pour la cannelle

    Directory of Open Access Journals (Sweden)

    Kathleen Bauer

    2008-12-01

    Full Text Available Depuis la nuit des temps, la cannelle a permis créer des liens entre les groupes en transmettant des traditions et un sentiment « d’appartenance ». Pourtant d’un autre point de vue, la cannelle a aussi mis en évidence les différences sociales à travers ses attributs liés au statut, au prestige et à l’exclusivité. Afin de trouver des réponses à ces questions de recherche, nous avons tenté de mieux comprendre les facteurs qui affectent la popularité de cette épice en nous référant à des sources aussi diverses que textes modernes et historiques, recettes de cuisine et entretiens. De nombreux auteurs expliquent la proéminence historique de la cannelle par ses propriétés « entremêlées » de façon unique : son sens symbolique, ses vertus pour la santé, son doux parfum et son goût. Toutefois, plus récemment dans l’Histoire, cette épice a perdu une grande partie de ses capacités à promouvoir l’exclusivité ou le prestige. Les informations collectées et présentées dans cet article permettent de mieux saisir les multiples façons dont les ingrédients culinaires peuvent créer des relations sociales et « connecter des vies ».From the earliest of times cinnamon has helped to bind groups together by imparting tradition and belonging. Yet on the other hand, cinnamon has evoked social difference through attributes of status, prestige and exclusivity. We have sought to find answers to fundamental research questions considering attributes affecting the popularity of this spice. Modern and historical text, recipes and some interview data were used to investigate this narrow topic. The authors attribute cinnamon’s historical prominence to uniquely intertwined properties of symbolic meaning, health benefits, sweet smell and taste. However, in recent history the spice has lost much of its ability to promote exclusivity or prestige. The collected information informs the understanding of the many ways food

  17. Guide pour la rédaction de cahiers des charges pour la sous-traitance en mécano-soudage

    CERN Document Server

    Cheminat, Olivier

    2016-01-01

    Ce rapport est principalement dédié aux rédacteurs de cahiers des charges lors de sous-traitance en soudage. Le choix de faire sous-traiter une fabrication et le choix du sous-traitant revêtent une triple dimension technique, économique et stratégique. Un sous-traitant n'est pas un simple fournisseur ; il est un véritable partenaire technique pour le donneur d'ordre qui lui confie la réalisation d'un produit qu'il a lui-même conçu. La sous-traitance nécessite alors, outre un audit préalable du partenaire, un suivi en continu, à distance, et une communication entre le donneur d'ordre et le sous-traitant. Le cahier des charges est un des éléments de cette communication. C'est un outil essentiel, notamment lorsque le marché est soumis à des normes, imposées par contrat entre le donneur d'ordre et le sous-traitant. Ce présent document est un guide pour la rédaction du document de consultation, afin d'être le plus précis et exhaustif possible, mais il ne saurait être utilisé pour établi...

  18. Un avenir ouvert pour une sociologie revisitée

    Directory of Open Access Journals (Sweden)

    Liliane Voyé

    2012-05-01

    Full Text Available Si l’on peut louer le souci de réflexivité qui anime la sociologie, il convient toutefois de dépasser ce stade du questionnement pour arriver à développer une sociologie moins inquiète d’elle-même. Les raisons de ce malaise sont diverses. Outre l’absence d’accord « sur un socle élémentaire de compétences exigibles » (François Dubet et Alain Caillé, la spécificité de son champ et de ses apports, comparée, par exemple, à l’histoire ou à la géographie, serait aussi une exigence importante, dont la rencontre la rendrait moins fragile. La question des méthodes qu’elle emploie mériterait également l’attention car celles-ci peuvent pécher par leurs faiblesses mais aussi parfois par leurs excès. L’objet même que se donne la sociologie appelle lui aussi une réflexion : la sociologie n’est pas du travail social frotté de science. Pourquoi dès lors privilégier l’étude des « problèmes sociaux » au sens courant du terme et ne pas s’intéresser aussi aux populations sans problème ou tout au moins se considérant comme telles ? Comme en médecine, les personnes saines aident à comprendre les maladies. À une époque où les changements se multiplient dans tous les domaines, la sociologie doit s’atteler à peaufiner sa conceptualisation et à repenser ses paradigmes, pour assumer pleinement son rôle social.An Open Future for a Revisited SociologyIf we can praise the concern for reflexivity that drives sociology, it should however go beyond the stage of questioning in order to develop a sociology that is less worried about itself. The reasons for this discomfort are various. Besides the lack of agreement « on the basis of elementary required skills » (François Dubet et Alain Caillé, the specificity of its field and its contributions, compared for example to history or geography, should also be an important requirement whose meeting would make it less fragile. The question of its methods

  19. Des terres pour l’agro-industrie internationale ? Un dilemme pour la politique foncière malgache

    Directory of Open Access Journals (Sweden)

    André Teyssier

    2010-02-01

    Full Text Available Les manœuvres d’appropriation foncière à grande échelle tentées fin 2008 par les entreprises Daewoo Logistics et Varun International, largement relayées par les médias et dénoncées par diverses organisations, ont participé à la déstabilisation du gouvernement Ravalomanana. Les montages de ces deux grands projets agro-industriels ont suivi des trajectoires différentes, l’un choisissant de contrôler d’immenses superficies par bail emphytéotique, l’autre privilégiant des formes de contractualisation de la production, mais tous deux ont été abandonnés face à des mouvements de contestation basés sur l’inaliénabilité de la « terre des ancêtres ». Le rejet de ces projets d’envergure encore inédite et en partie tournés vers des cultures d’exportation est compréhensible tant les retombées économiques et sociales paraissaient incertaines. Madagascar ne saurait néanmoins se priver d’investissements dans le secteur agricole, mais des choix de développement, orientés par une meilleure connaissance des processus en cours, restent à opérer en toute transparence, afin de combiner développement de l’agro-business et promotion des exploitations familiales. Pour l’instant, ces incertitudes marquent une politique foncière qui, même rénovée, hésite entre la formalisation de droits sur le sol au profit du plus grand nombre grâce à une décentralisation de la gestion foncière et l’octroi de vastes espaces à des firmes internationales suivant des procédures accélérées.

  20. Utilisation du test GeneXpert pour le diagnostic de la tuberculose au ...

    African Journals Online (AJOL)

    Utilisation du test GeneXpert pour le diagnostic de la tuberculose au service des maladies infectieuses du CHNU de Fann. Sylvie Audrey Diop, Aminata Massaly, Daye Ka, Noel Magloire Manga, Louise Fortes-Déguénonvo, Cheikh Tidiane Ndour, Viviane Marie Pierre Cisse, Moussa Seydi ...

  1. Pour on application of growth promoters in veal calves: analytical and histological results

    NARCIS (Netherlands)

    Schilt, R.; Groot, M.J.; Berende, P.L.M.; Rammazza, V.; Ossenkoppele, J.S.; Haasnoot, W.; Bennekom, van E.O.; Brouwer, L.; Hooijerink, H.

    1998-01-01

    To investigate the possibilities for screening and confirmation methods when the 'pour on' method of application is used for administration of growth promoters, an animal experiment was performed using a cocktail of a combination of growth promoters derived from (illegal) practice. Two cocktails

  2. : tous les projets | Page 226 | CRDI - Centre de recherches pour le ...

    International Development Research Centre (IDRC) Digital Library (Canada)

    Plus de 700 millions de personnes dépendent de systèmes d'aquaculture pour gagner leur vie. Sujet: AGRICULTURE. Région: Central Asia, Far East Asia, South Asia, South of Sahara. Programme: Agriculture and Food Security. Financement total : CA$ 4,200,000.00. Soutien au programme de recherche du GCRAI sur les ...

  3. Résultats de recherche | Page 6 | CRDI - Centre de recherches pour ...

    International Development Research Centre (IDRC) Digital Library (Canada)

    Adaptation aux changements climatiques et innovation de l'aquaculture sur le Mékong – AQUADAPT Mékong. L'aquaculture est un secteur économique important, un moyen de subsistance et un contributeur de résilience pour les systèmes alimentaires dans la région du Mékong.

  4. Partenariat pour l'adaptation des populations vulnérables à la ...

    International Development Research Centre (IDRC) Digital Library (Canada)

    Projet Partenariat Multi-acteurs pour l'Adaptation des Populations Vulnérables à la Salinisation des sols induite par les Changements Climatiques au Sénégal : rapport final (18 mars 2009 - 31 mars 2012). Download PDF ... New website will help record vital life events to improve access to services for all. A new website and ...

  5. : tous les projets | Page 81 | CRDI - Centre de recherches pour le ...

    International Development Research Centre (IDRC) Digital Library (Canada)

    Région: North of Sahara, South of Sahara, Central Asia, Far East Asia, South Asia, Europe, North and Central America, South America, Brazil, Nepal, Nigeria. Programme: Networked Economies. Financement total : CA$ 4,226,848.00. Le partenariat mondial sur les données ouvertes pour le développement. Projet.

  6. Ce que nous faisons | Page 68 | CRDI - Centre de recherches pour ...

    International Development Research Centre (IDRC) Digital Library (Canada)

    Le CRDI appuie des travaux de recherche dans les pays en voie de développement en vue de produire un changement réel et durable. Ce savoir peut servir d'outil pour résoudre des problèmes mondiaux urgents. Nous partageons ce savoir avec les autres en :

  7. Ce que nous faisons | Page 17 | CRDI - Centre de recherches pour ...

    International Development Research Centre (IDRC) Digital Library (Canada)

    Cohérence de la prévention des maladies non transmissibles et des politiques agroalimentaires en Argentine. L'alimentation malsaine est largement reconnue comme un facteur de risque majeur pour les maladies non transmissibles (MNT). Argentine, Amérique Nord Et Centrale, Amérique Du Sud. PROJECT ...

  8. : tous les projets | Page 288 | CRDI - Centre de recherches pour le ...

    International Development Research Centre (IDRC) Digital Library (Canada)

    Sujet: TRAINING PROGRAMMES, ENVIRONMENTAL HEALTH, POLITICIANS, DECISION MAKING, POLICY MAKING. Région: Benin, Ivory Coast, Senegal, North of Sahara, South of Sahara. Programme: Alimentation, environnement et santé. Financement total : CA$ 230,700.00. Programme de leadership pour favoriser ...

  9. Beethoven, Ludwig van: Concerto pour violon op. 61 / Jean-Michel Molkhou

    Index Scriptorium Estoniae

    Molkhou, Jean-Michel

    1997-01-01

    Uuest heliplaadist "Beethoven, Ludwig van: Concerto pour violon op. 61 (cadence Schnittke). Les 2 Romances op. 40 et 50. Orchestre Symphonique National d'Estonie, Arvo Volmer" Globe GLO 5155, distribution Talis (CD:153F). 1996. TT:1h 01'56"

  10. Le SIPAZ, ou journalisme pour la paix en Colombie | CRDI - Centre ...

    International Development Research Centre (IDRC) Digital Library (Canada)

    15 juil. 2011 ... À la suite de ces attaques contre le milieu social et culturel du pays, un groupe ... le SIPAZ — Sistema de Comunicación para la Paz (ou Système de ... ont établi des directives pour la gestion des nouvelles dans un guide de ...

  11. : tous les projets | Page 479 | CRDI - Centre de recherches pour le ...

    International Development Research Centre (IDRC) Digital Library (Canada)

    Sujet: HEALTH SURVEYS, HEALTH STATISTICS, DATA COLLECTING, INFORMATION TECHNOLOGY, COMPUTERS. Région: Bangladesh, India, Viet Nam, Tanzania, Canada. Programme: Fondements pour l'innovation. Financement total : CA$ 65,200.00. Health Bridge - Les TIC au profit de la cueillette et de la gestion ...

  12. : tous les projets | Page 430 | CRDI - Centre de recherches pour le ...

    International Development Research Centre (IDRC) Digital Library (Canada)

    Région: Middle East, North of Sahara, South of Sahara, Central Asia, Far East Asia, South Asia, Iran, Iraq, Jordan, Lebanon, Morocco, Syria, Egypt, Palestine, Israel. Programme: Fondements pour l'innovation. Financement total : CA$ 500,000.00. Gouvernance, réformes et islamisme au Moyen-Orient et en Afrique du Nord.

  13. : tous les projets | Page 431 | CRDI - Centre de recherches pour le ...

    International Development Research Centre (IDRC) Digital Library (Canada)

    Région: Middle East, North of Sahara, South of Sahara, Central Asia, Far East Asia, South Asia, Iran, Iraq, Jordan, Lebanon, Morocco, Syria, Egypt, Palestine, Israel. Programme: Fondements pour l'innovation. Financement total : CA$ 500,000.00. Gouvernance, réformes et islamisme au Moyen-Orient et en Afrique du Nord.

  14. Santé | CRDI - Centre de recherches pour le développement ...

    International Development Research Centre (IDRC) Digital Library (Canada)

    Can music make us better at math? An Israeli-Canadian research team is trying to find out. Read more about When the brain hits the right notes. Langue English. Le CRDI vise à favoriser des changements positifs à long terme pour les personnes qui en ont le plus besoin. Cependant, ce sont les réalisations annuelles qui ...

  15. India : tous les projets | Page 10 | CRDI - Centre de recherches pour ...

    International Development Research Centre (IDRC) Digital Library (Canada)

    Région: India, Far East Asia, Philippines, Thailand, Central Asia, South Asia ... Ces dernières, en effet, ont privilégié les cultures de rente et les céréales ... à la vie politique en Inde - utilisent-elles la voie parlementaire pour se faire entendre ?

  16. : tous les projets | Page 45 | CRDI - Centre de recherches pour le ...

    International Development Research Centre (IDRC) Digital Library (Canada)

    Région: Kenya, Malawi, Zimbabwe, Uganda, Tanzania, Zambia, Netherlands. Programme: Employment and Growth. Financement total : CA$ 1,213,000.00. Accroître l'inclusion financière pour les femmes et les jeunes vulnérables : Proyecto Capital. Projet. L'accès à des services financiers officiels peut aider les personnes ...

  17. Changements à la tête du CERN - Robert Aymar aux commandes pour 5 ans.

    CERN Multimedia

    2003-01-01

    "Une nouvelle équipe prendra les rênes du CERN à partir du 1er janvier. Le Francais Robert Aymar, anciennement directeur du Projet de reacteur thermonucleaire experimental international (ITER), dirigera le centre de recherche pour la periode 2004-2008" (1 page).

  18. Nanotechnologies et Génie Civil, comment coopérer pour innover ?

    OpenAIRE

    LEBENTAL, Bérengère

    2010-01-01

    On discute la gestion de projet innovant à partir de l'exemple du projet Nanosonar, un projet de coopération entre le CEA-LETI et le LCPC visant au développement de nanocapteur innovant pour le suivi de durabilité en génie civil.

  19. Fonds d'innovation pour le développement (FID) aux fins de la ...

    International Development Research Centre (IDRC) Digital Library (Canada)

    innovation en santé dans le but d'améliorer les conditions de vie des pauvres dans le monde entier. Le Fonds d'innovation pour le développement (FID) appuiera des scientifiques et des établissements voués à la recherche en santé par le ...

  20. : tous les projets | Page 623 | CRDI - Centre de recherches pour le ...

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    Sujet: CERAMICS INDUSTRY, POTTERY, AIR POLLUTION, ENVIRONMENTAL HEALTH, INCOME GENERATION. Région: India, Central Asia, Far East Asia, South Asia. Programme: Alimentation, environnement et santé. Financement total : CA$ 300,000.00. Atténuation des risques pour la santé dans le secteur de la ...

  1. Fils RSS | CRDI - Centre de recherches pour le développement ...

    International Development Research Centre (IDRC) Digital Library (Canada)

    Cliquez sur le fil pour ajouter votre site ou votre lecteur RSS préféré Fil de financement du CRDI Fil des nouvelles du CRDI Fil des perspectives du CRDI Fil des projets du CRDI Fil des publications du CRDI.

  2. Ce que nous avons à offrir | CRDI - Centre de recherches pour le ...

    International Development Research Centre (IDRC) Digital Library (Canada)

    Le CRDI offre un environnement de travail stimulant dans lequel gravitent des gens qui partagent votre passion pour le développement international. Nous offrons des occasions continues d'apprentissage et de perfectionnement personnel sous la forme de conférences, de forums, de présentations et d'ateliers en ...

  3. Administrateur du système (h/f) | CRDI - Centre de recherches pour ...

    International Development Research Centre (IDRC) Digital Library (Canada)

    Sous la supervision du gestionnaire, Infrastructure, sécurité et documents (ISD), ... et de la maintenance courants des divers systèmes d'infrastructure du Centre, ... techniques dans les régions et des techniciens sous contrat) pour fournir des ...

  4. Document de recherche 4 – Institutions pour la gestion efficace de la ...

    International Development Research Centre (IDRC) Digital Library (Canada)

    , elle n'est pas encore assez ancrée sur le plan politique pour être mise en application, malgré ce que laissent entendre les données probantes. Ce présent document est le quatriéme dans la série de documents de ...

  5. L'efficacité de la recherche-action participative pour les ...

    International Development Research Centre (IDRC) Digital Library (Canada)

    La recherche-action participative (RAP) est une approche qui convient parfaitement au mandat de recherche et de renforcement des capacités du programme ... La méthode de RAP se prête bien à un leadership. ▻ assumé par des chercheurs atypiques. Certains projets montrent clairement que, pour les. ▻ décideurs, les ...

  6. Bolivie | CRDI - Centre de recherches pour le développement ...

    International Development Research Centre (IDRC) Digital Library (Canada)

    De 2002 à 2007, nous avons soutenu un projet collaboratif entre le Canada et la Bolivie dans le cadre duquel une méthode participative permettant de cartographier les ... Femmes appuyant les femmes : l'engagement civique en réseau pour promouvoir un leadership efficace des femmes dans l'élaboration de politiques.

  7. : tous les projets | Page 598 | CRDI - Centre de recherches pour le ...

    International Development Research Centre (IDRC) Digital Library (Canada)

    Sujet: GOVERNMENT, CORRUPTION, ECONOMIC IMPLICATIONS, ADMINISTRATIVE REFORM, INSTITUTION BUILDING. Région: Central Asia, Far East Asia, South Asia, Pakistan. Programme: Emploi et croissance. Financement total : CA$ 296,600.00. Les institutions pour la reddition de comptes à la population au ...

  8. Ce que nous faisons | Page 122 | CRDI - Centre de recherches pour ...

    International Development Research Centre (IDRC) Digital Library (Canada)

    Le CRDI finance des études de recherche dans les pays en voie de développement en vue de produire un changement durable à grande échelle. Pour que le savoir devienne un outil permettant de résoudre des problèmes urgents :

  9. Ce que nous faisons | Page 47 | CRDI - Centre de recherches pour ...

    International Development Research Centre (IDRC) Digital Library (Canada)

    Le CRDI appuie des travaux de recherche dans les pays en voie de développement en vue de produire un changement réel et durable. Ce savoir peut servir d'outil pour résoudre des problèmes mondiaux urgents. Nous partageons ce savoir avec les autres en :

  10. nigéria : tous les projets | CRDI - Centre de recherches pour le ...

    International Development Research Centre (IDRC) Digital Library (Canada)

    ... des gouvernements étrangers ont eu des effets économiques positifs tout comme ... L'accès à Internet est devenu une priorité pour les pays en développement. ... les régions rurales mal desservies du Nigeria grâce à la recherche visant la ...

  11. : tous les projets | Page 491 | CRDI - Centre de recherches pour le ...

    International Development Research Centre (IDRC) Digital Library (Canada)

    Sujet: INFORMATION TECHNOLOGY, FINANCIAL MANAGEMENT, FINANCIAL INSTITUTIONS, CREDIT COOPERATIVES. Région: Kenya, Tanzania, Uganda, North of Sahara, South of Sahara. Financement total : CA$ 250,400.00. OASIS : une architecture, des normes et des systèmes d'information libres pour les services ...

  12. Circuit court du marché des produits agricoles : pour une gestion ...

    African Journals Online (AJOL)

    pour un développement durable au Lac Alaotra. . Cirad-Inra-SupAgro,. Montpellier, FR. Available at . Penot, É., Dabat, M.-H., Rakotoarimanana, A. & Grandjean, P. 2014. L'évolution des pratiques agricoles au lac Alaotra à Madagascar. Une approche par les temporalités.

  13. Rapport de frais de 2016-2017 pour Sophie D'Amours | IDRC ...

    International Development Research Centre (IDRC) Digital Library (Canada)

    Rapport de frais de 2016-2017 pour Sophie D'Amours. What we do · Funding · Resources · About IDRC. Knowledge. Innovation. Solutions. Careers · Contact Us · Site map. Sign up now for IDRC news and views sent directly to your inbox each month. Subscribe · Copyright · Open access policy · Privacy policy · Research ...

  14. kenya : tous les projets | Page 9 | CRDI - Centre de recherches pour ...

    International Development Research Centre (IDRC) Digital Library (Canada)

    efficacité des interventions à caractère électronique pour ce qui est de relier les agriculteurs africains aux marchés (eARN Africa). Projet. Les études semblent indiquer que les technologies de l'information et de la communication (TIC) comportent ...

  15. Le débat des semences volume 2 : Solutions pour les lois ...

    International Development Research Centre (IDRC) Digital Library (Canada)

    Le Débat des semences met les lecteurs au courant de ce qui a changé — sur le ... pour les lois nationales régissant le contrôle des ressources génétiques et des ... IWRA/CRDI sur les changements climatiques et la gestion adaptive de l'eau.

  16. egypt : tous les projets | Page 4 | CRDI - Centre de recherches pour ...

    International Development Research Centre (IDRC) Digital Library (Canada)

    TIC pour le développement des micros, petites et moyennes entreprises égyptiennes. Projet. La compétitivité des entreprises égyptiennes est reconnue ... Sujet: PRIMARY EDUCATION, SCIENCE EDUCATION, TEACHING AIDS, Internet, INFORMATION TECHNOLOGY. Région: Egypt, North of Sahara, South of Sahara.

  17. Ce que nous faisons | Page 36 | CRDI - Centre de recherches pour ...

    International Development Research Centre (IDRC) Digital Library (Canada)

    Le CRDI appuie des travaux de recherche dans les pays en voie de développement en vue de produire un changement réel et durable. Ce savoir peut servir d'outil pour résoudre des problèmes mondiaux urgents. Nous partageons ce savoir avec les autres en :

  18. Journal des Sciences Pour l'Ingénieur - Vol 12 (2010)

    African Journals Online (AJOL)

    DOWNLOAD FULL TEXT DOWNLOAD FULL TEXT. M Pasquinelli, D Maestre, K Lagha, D Barakel, J Le Rouzo, C Alfonso, O Palais ... Modele electrique d'une pile a combustible « pem » pour utilisation electronique de puissance · EMAIL FULL TEXT EMAIL FULL TEXT DOWNLOAD FULL TEXT DOWNLOAD FULL TEXT.

  19. Nouvelles et activités | Page 6 | CRDI - Centre de recherches pour le ...

    International Development Research Centre (IDRC) Digital Library (Canada)

    Consultez les nouvelles et les activités. Utilisez cet outil de recherche pour trouver des nouvelles ou des activités précis dans le site Web du CRDI. Content type. Tout. Activités. Avis aux médias. Bulletins. Communiqués. Nouvelle ...

  20. Nouvelles et activités | Page 2 | CRDI - Centre de recherches pour le ...

    International Development Research Centre (IDRC) Digital Library (Canada)

    Consultez les nouvelles et les activités. Utilisez cet outil de recherche pour trouver des nouvelles ou des activités précis dans le site Web du CRDI. Content type. Tout. Activités. Avis aux médias. Bulletins. Communiqués. Nouvelle ...

  1. Nouvelles et activités | Page 7 | CRDI - Centre de recherches pour le ...

    International Development Research Centre (IDRC) Digital Library (Canada)

    Consultez les nouvelles et les activités. Utilisez cet outil de recherche pour trouver des nouvelles ou des activités précis dans le site Web du CRDI. Content type. Tout. Activités. Avis aux médias. Bulletins. Communiqués. Nouvelle ...

  2. Nouvelles et activités | Page 5 | CRDI - Centre de recherches pour le ...

    International Development Research Centre (IDRC) Digital Library (Canada)

    Consultez les nouvelles et les activités. Utilisez cet outil de recherche pour trouver des nouvelles ou des activités précis dans le site Web du CRDI. Content type. Tout. Activités. Avis aux médias. Bulletins. Communiqués. Nouvelle ...

  3. : tous les projets | Page 39 | CRDI - Centre de recherches pour le ...

    International Development Research Centre (IDRC) Digital Library (Canada)

    Malgré des garanties constitutionnelles, la violence au sein et à l'extérieur du foyer constitue une menace omniprésente et une réalité quotidienne pour une grande majorité de femmes et de filles en Inde. Sujet: VIOLENCE. Région: India. Programme: Governance and Justice. Financement total : CA$ 799,800.00.

  4. Ce que nous faisons | Page 39 | CRDI - Centre de recherches pour ...

    International Development Research Centre (IDRC) Digital Library (Canada)

    Le CRDI appuie des travaux de recherche dans les pays en voie de développement en vue de produire un changement réel et durable. Ce savoir peut servir d'outil pour résoudre des problèmes mondiaux urgents. Nous partageons ce savoir avec les autres en :

  5. Agent d'approvisionnement (h/f) | CRDI - Centre de recherches pour ...

    International Development Research Centre (IDRC) Digital Library (Canada)

    approvisionnement a pour rôle et pouvoirs d'obtenir des biens et des services au nom du CRDI ... Analyser les besoins du client, conseiller et orienter le client et sa famille quant à ce à quoi ils ont droit en vertu de la politique du CRDI en matière de ...

  6. Jeunes agripreneurs : Élargir les possibilités pour les jeunes dans le ...

    International Development Research Centre (IDRC) Digital Library (Canada)

    activités agro-alimentaires en vue d'assurer la transformation agricole et l'emploi des jeunes en Afrique. Ce projet déterminera, élaborera et mettra à l'essai sur le terrain des modèles d'entreprise créatifs et audacieux pour aider les jeunes ...

  7. Conducts of disinfection, pouring and storage of irreversible hydrocolloid impressions by undergraduate students

    Directory of Open Access Journals (Sweden)

    Thalisson Saymo de Oliveira SILVA

    Full Text Available Abstract Introduction Obtaining dental models that accurately represent the molded oral tissue requires professional attention, especially when using irreversible hydrocolloid as a molding material. Objective To evaluate the conducts of undergraduate dental students at different internships for the disinfecting procedures, pouring, and storage of irreversible hydrocolloid impressions. Material and method This is an observational, cross-sectional and descriptive study with a census sample of 89 students enrolled in the supervised internships I, II, III and IV. Data collection was performed using a structured questionnaire containing eight questions. Data were analyzed at the 5% significance level. Result Most of the students (88.8% performed the disinfection procedure, for which the most widely used method (64.6% was the application of sodium hypochlorite 1% spray stored in a sealed container. The most common disinfection time was 10 minutes (86.1%. Students in the early internships performed better in regard to the proportion of water/plaster to be used compared with students in the final internships. At all internships, pouring and storage of the ensemble of mold and model were neglected during the setting reaction. There was a statistically significant association between the stage and the disinfection method, the ratio of water/powder and pouring of the model (p<0.05. Conclusion Students exhibited appropriate conduct of disinfection; however, they should be encouraged to use evidence-based clinical practices in order to improve the procedures of pouring and storage of irreversible hydrocolloid molds.

  8. : tous les projets | Page 133 | CRDI - Centre de recherches pour le ...

    International Development Research Centre (IDRC) Digital Library (Canada)

    Les think tanks des pays en développement cherchent à influer sur les politiques pour contribuer à améliorer les conditions de vie des populations. Date de début : 17 mai 2013. End Date: 17 juin 2014. Sujet: DEVELOPING COUNTRIES, POLICY MAKING, INTERVIEWS, CASE STUDIES, CROSS CULTURAL ANALYSIS, ...

  9. Ce que nous faisons | Page 145 | CRDI - Centre de recherches pour ...

    International Development Research Centre (IDRC) Digital Library (Canada)

    Le CRDI appuie des travaux de recherche dans les pays en voie de développement en vue de produire un changement réel et durable. Ce savoir peut servir d'outil pour résoudre des problèmes mondiaux urgents. Nous partageons ce savoir avec les autres en :

  10. Transformation des découvertes en génomique pour soigner les ...

    International Development Research Centre (IDRC) Digital Library (Canada)

    ... des composés préventifs et thérapeutiques ciblés pour des essais précliniques ... IDRC is pleased to announce the results of its 2017 call for proposals to establish Cyber ... IDRC invites applications for the IDRC Doctoral Research Awards.

  11. Journal des Sciences Pour l'Ingénieur - Vol 5 (2005)

    African Journals Online (AJOL)

    Utilisation de modèles réduits pour l\\'étude et la simulation des systèmes de mise à la ... study in modelling: capacitance and space charge region width determination ... Damage process in a discrete disordered model and consequences on ...

  12. Ce que nous faisons | Page 25 | CRDI - Centre de recherches pour ...

    International Development Research Centre (IDRC) Digital Library (Canada)

    Le CRDI appuie des travaux de recherche dans les pays en voie de développement en vue de produire un changement réel et durable. Ce savoir peut servir d'outil pour résoudre des problèmes mondiaux urgents. Nous partageons ce savoir avec les autres en :

  13. Tanzanie | CRDI - Centre de recherches pour le développement ...

    International Development Research Centre (IDRC) Digital Library (Canada)

    Un nouveau modèle pour optimiser l'impact de la recherche et de l'innovation. Read more about Mise à l'échelle de la science. Langue French. A new model for optimizing the impact of research and innovation. Read more about Scaling Science. Langue English. Read more about Emploi des jeunes et autonomisation ...

  14. india : tous les projets | Page 11 | CRDI - Centre de recherches pour ...

    International Development Research Centre (IDRC) Digital Library (Canada)

    Sujet: PEACE RESEARCH, WAR, VIOLENCE, PSYCHOLOGICAL ASPECTS. Région: India, Ireland. Programme: Gouvernance et justice. Financement total : CA$ 527,600.00. Droits génésiques et préférence pour les garçons en Inde - mobilisation des ressources. Projet. Ce projet vise à analyser deux manifestations des ...

  15. Rapport financier trimestriel pour le trimestre qui a pris fin le 31

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    Office 2004 Test Drive User

    31 déc. 2015 ... Le CRDI finance des travaux de recherche appliquée ... recherches pour le développement international (CRDI, le Centre) et ..... voie de développement et sur la mise en oeuvre des connaissances scientifiques, techniques et autres en .... Les accords expirent à des dates différentes, et le dernier prend fin.

  16. pour le trimestre qui a pris fin le 30 juin 2015

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    Office 2004 Test Drive User

    30 juin 2015 ... Le CRDI finance des travaux de recherche appliquée ... recherches pour le développement international (le Centre) et de ..... voie de développement et sur la mise en oeuvre des connaissances scientifiques, techniques et autres en .... Les accords expirent à des dates différentes, et le dernier prend fin en.

  17. pour le trimestre qui a pris fin le 31 décembre 2014

    International Development Research Centre (IDRC) Digital Library (Canada)

    Office 2004 Test Drive User

    31 déc. 2014 ... Le CRDI finance des travaux de recherche appliquée ... recherches pour le développement international (le Centre) et de ...... voie de développement et sur la mise en oeuvre des connaissances scientifiques, techniques et autres en vue .... Les accords expirent à des dates différentes, et le dernier prend fin.

  18. Rapport financier trimestriel pour le trimestre qui a pris fin le 30

    International Development Research Centre (IDRC) Digital Library (Canada)

    Office 2004 Test Drive User

    30 sept. 2015 ... Le CRDI finance des travaux de recherche appliquée ... recherches pour le développement international (le Centre) et de ..... voie de développement et sur la mise en oeuvre des connaissances scientifiques, techniques et autres en .... Les accords expirent à des dates différentes, et le dernier prend fin en.

  19. : tous les projets | Page 395 | CRDI - Centre de recherches pour le ...

    International Development Research Centre (IDRC) Digital Library (Canada)

    Les études semblent indiquer que les technologies de l'information et de la communication (TIC) comportent un certain nombre d'avantages pour les agriculteurs. Date de début : 31 mars 2009. End Date: 22 juin 2012. Sujet: SURVEYS, SMALLHOLDERS, INFORMATION TECHNOLOGY, Internet, AGRICULTURAL ...

  20. Risques et possibilités liés aux changements climatiques pour les ...

    International Development Research Centre (IDRC) Digital Library (Canada)

    ... aussi d'évaluer le potentiel que représentent ces marchés innovants pour inciter les ... de un Nuevo Sector en la Economía Sistema B. Institution Country. Chile ... IDRC “unpacks women's empowerment” at McGill University Conference.

  1. Sud du Sahara | Page 59 | CRDI - Centre de recherches pour le ...

    International Development Research Centre (IDRC) Digital Library (Canada)

    Sud du Sahara. Sud du Sahara. Read more about Health Financing and Benefit Incidence Analysis in Uganda and Zambia. Langue English. Read more about Le Centre d'innovation pour la résilience de l'Afrique de l'Est. Langue French. Read more about Climate Change and Water Adaptation Options. Langue English.

  2. Actualités en matière antique: pour Emmanuèle Baumgartner

    Directory of Open Access Journals (Sweden)

    Carlos Pérez Varela

    2007-04-01

    Full Text Available À propos de l’œuvre de Laurence Harf-Lancner, Laurence Mathey-Maille et Michelle Szkilnik (2006: Conter de Troie et d'Alexandre: pour Emmanuèle Baumgartner (Paris, Editions Presses Sorbonne Nouvelle, 308 pp., 12 pl., ISBN 2878543599.

  3. Ce que nous faisons | Page 26 | CRDI - Centre de recherches pour ...

    International Development Research Centre (IDRC) Digital Library (Canada)

    Le CRDI appuie des travaux de recherche dans les pays en voie de développement en vue de produire un changement réel et durable. Ce savoir peut servir d'outil pour résoudre des problèmes mondiaux urgents. Nous partageons ce savoir avec les autres en :

  4. Ce que nous faisons | Page 50 | CRDI - Centre de recherches pour ...

    International Development Research Centre (IDRC) Digital Library (Canada)

    Le CRDI appuie des travaux de recherche dans les pays en voie de développement en vue de produire un changement réel et durable. Ce savoir peut servir d'outil pour résoudre des problèmes mondiaux urgents. Nous partageons ce savoir avec les autres en :

  5. : tous les projets | Page 343 | CRDI - Centre de recherches pour le ...

    International Development Research Centre (IDRC) Digital Library (Canada)

    Sujet: SMALL ENTERPRISES, MEDIUM ENTERPRISES, RESEARCH POLICY, RESEARCH AND DEVELOPMENT. Région: Central Asia, Far East Asia, South Asia, Malaysia, Thailand, Taiwan, Singapore. Programme: Économies en réseaux. Financement total : CA$ 309,900.00. Élaboration de politiques efficaces pour le ...

  6. : tous les projets | Page 71 | CRDI - Centre de recherches pour le ...

    International Development Research Centre (IDRC) Digital Library (Canada)

    Ce projet traitera des effets de la croissance économique rapide dans la région du bassin du Mékong sur les emplois pour les jeunes. Région: Cambodia, China, Laos, Myanmar, Thailand, Viet Nam, Malaysia, Philippines, Brunei, Singapore. Programme: Employment and Growth. Financement total : CA$ 1,029,600.00.

  7. Chef de programme (h/f) | CRDI - Centre de recherches pour le ...

    International Development Research Centre (IDRC) Digital Library (Canada)

    Se charger de l'orientation stratégique globale de l'IP;; Préparer le prospectus de ... Se charger du recrutement et du perfectionnement professionnel des ... projet;; Négocier avec des chercheurs et des responsables de politiques pour qu'ils ...

  8. Soutien organisationnel pour la phase 2 de l'ITT : Centre for Budget ...

    International Development Research Centre (IDRC) Digital Library (Canada)

    Soutien organisationnel pour la phase 2 de l'ITT : Centre for Budget and Governance Accountability. Ce financement contribuera à renforcer le rôle du Centre for Budget and Governance Accountability (CBGA) en tant qu'organisme crédible de recherche sur les politiques publiques en Inde en renforçant sa capacité à ...

  9. Bulletin #114 | CRDI - Centre de recherches pour le dévelopement ...

    International Development Research Centre (IDRC) Digital Library (Canada)

    Le CRDI annonce la gagnante de la prestigieuse bourse de recherche Bentley · Annonce des gagnants de l'appel à propositions de l'initiative Résilience des villes · Le CRDI et BetterEvaluation lancent un guide interactif pour la gestion des évaluations · Le vaccin canadien contre le virus Ebola entre dans une nouvelle ...

  10. : tous les projets | Page 410 | CRDI - Centre de recherches pour le ...

    International Development Research Centre (IDRC) Digital Library (Canada)

    Le Consejo Nicaragüense de Ciencia y Tecnologia (CONICYT) a pour mandat de coordonner les différents acteurs du système d'innovation national du Nicaragua. Date de début : 21 novembre 2008. End Date: 21 novembre 2010. Sujet: SCIENCE AND TECHNOLOGY POLICY, SCIENTIFIC COOPERATION, RESEARCH ...

  11. Résultats de recherche | Page 7 | CRDI - Centre de recherches pour ...

    International Development Research Centre (IDRC) Digital Library (Canada)

    Vers une politique nationale en matière de sciences et de technologies au Nicaragua. Le Consejo Nicaragüense de Ciencia y Tecnologia (CONICYT) a pour mandat de coordonner les différents acteurs du système d'innovation national du Nicaragua. Projet.

  12. : tous les projets | Page 412 | CRDI - Centre de recherches pour le ...

    International Development Research Centre (IDRC) Digital Library (Canada)

    Le Consejo Nicaragüense de Ciencia y Tecnologia (CONICYT) a pour mandat de coordonner les différents acteurs du système d'innovation national du Nicaragua. Date de début : 21 novembre 2008. End Date: 21 novembre 2010. Sujet: SCIENCE AND TECHNOLOGY POLICY, SCIENTIFIC COOPERATION, RESEARCH ...

  13. Ce que nous faisons | Page 118 | CRDI - Centre de recherches pour ...

    International Development Research Centre (IDRC) Digital Library (Canada)

    Le CRDI finance des études de recherche dans les pays en voie de développement en vue de produire un changement durable à grande échelle. Pour que le savoir devienne un outil permettant de résoudre des problèmes urgents :

  14. Nouveau partenariat pour le développement de l'Afrique | CRDI ...

    International Development Research Centre (IDRC) Digital Library (Canada)

    22 juil. 2011 ... Devant elle, la promesse d'un avenir meilleur lui est offerte par le Nouveau partenariat pour le développement de l'Afrique (NEPAD), un plan radical qui offre ... Les populations africaines réclament de vraies élections, un débat public plus libre et un gouvernement plus responsable et respectueux des lois.

  15. Sud du Sahara | Page 63 | CRDI - Centre de recherches pour le ...

    International Development Research Centre (IDRC) Digital Library (Canada)

    Read more about Civil Society and Public Powers : Partners for Social Economy and Solidarity. Langue English. Read more about Société civile et pouvoirs publics : Partenaires pour une économie sociale et solidaire. Langue French. Read more about Renforcement des capacités en analyse des politiques et systèmes de ...

  16. Institut pour la connectivité dans les Amériques (ICA) - phase II ...

    International Development Research Centre (IDRC) Digital Library (Canada)

    L'Institut pour la connectivité dans les Amériques a mené à bien plus de 70 ... par le truchement des TIC en se concentrant sur trois thèmes : la cyberparticipation des ... ont grandement aidé à mieux faire comprendre l'utilisation et l'intégration.

  17. Ce que nous faisons | Page 93 | CRDI - Centre de recherches pour ...

    International Development Research Centre (IDRC) Digital Library (Canada)

    Le CRDI finance des études de recherche dans les pays en voie de développement en vue de produire un changement durable à grande échelle. Pour que le savoir devienne un outil permettant de résoudre des problèmes urgents :

  18. Ce que nous faisons | Page 52 | CRDI - Centre de recherches pour ...

    International Development Research Centre (IDRC) Digital Library (Canada)

    Le CRDI finance des études de recherche dans les pays en voie de développement en vue de produire un changement durable à grande échelle. Pour que le savoir devienne un outil permettant de résoudre des problèmes urgents :

  19. Ce que nous faisons | Page 165 | CRDI - Centre de recherches pour ...

    International Development Research Centre (IDRC) Digital Library (Canada)

    Le CRDI finance des études de recherche dans les pays en voie de développement en vue de produire un changement durable à grande échelle. Pour que le savoir devienne un outil permettant de résoudre des problèmes urgents :

  20. Ce que nous faisons | Page 8 | CRDI - Centre de recherches pour le ...

    International Development Research Centre (IDRC) Digital Library (Canada)

    Le CRDI finance des études de recherche dans les pays en voie de développement en vue de produire un changement durable à grande échelle. Pour que le savoir devienne un outil permettant de résoudre des problèmes urgents :