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1.
Respiration ; 89(2): 119-26, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-25633753

RESUMO

BACKGROUND: The link between organizing pneumonia (OP) and gastroesophageal reflux disease (GERD) is not well known. There is little evidence in the literature to establish a causal link between GERD and OP. OBJECTIVES: The aim of the study was to assess the hypothesis that OP is more severe when it is associated with GERD and that it leads to more frequent relapses. METHODS: In a retrospective study on 44 patients suffering from OP, we compared the clinical, radiological and histological characteristics of 2 groups, 1 composed of patients with GERD (n = 20) and the other of patients without GERD (n = 24). RESULTS: The GERD group was distinguished by a higher number of patients with migratory alveolar opacities on chest radiography and thoracic computerized tomography (14/20 vs. 9/24; p = 0.03 and 18/20 vs. 13/24; p = 0.01), greater hypoxemia [60 (42-80) vs. 70 (51-112) mm Hg; p = 0.03], greater bronchoalveolar lavage cellularity [0.255 (0.1-1.8) vs. 0.150 (0.05-0.4) g/l; p = 0.035] and more frequent relapses (14/20 vs. 9/24; p = 0.03). CONCLUSIONS: OP associated with GERD is more severe and results in more frequent relapses. Microinhalation of gastric secretions might induce lung inflammation leading to OP and relapse. We suggest that typical symptoms of GERD such as pyrosis should be investigated in OP.


Assuntos
Pneumonia em Organização Criptogênica/complicações , Refluxo Gastroesofágico/complicações , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva , Estudos Retrospectivos , Fatores de Risco
2.
Pharm Res ; 28(9): 2147-56, 2011 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-21491145

RESUMO

PURPOSE: Lung cancer is the leading cause of cancer-related death worldwide. The efficacy of current systemic treatments is limited, with major side effects and only modest survival improvements. Aerosols routinely used to deliver drugs into the lung for treating infectious and inflammatory lung diseases have never been used to deliver monoclonal antibodies to treat lung cancer. We have shown that cetuximab, a chimeric anticancer anti-EGFR mAb, is suitable for airway delivery as it resists the physical constraints of aerosolization, and have evaluated the aerosol delivery of cetuximab in vivo. METHODS: We developed an animal model of lung tumor sensitive to cetuximab by injecting Balb/c Nude mice intratracheally with A431 cells plus 10 mM EDTA and analyzed the distribution, pharmacokinetics and antitumor efficacy of cetuximab aerosolized into the respiratory tract. RESULTS: Aerosolized IgG accumulated durably in the lungs and the tumor, but passed poorly and slowly into the systemic circulation. Aerosolized cetuximab also limited the growth of the mouse tumor. Thus, administering anticancer mAbs via the airways is effective and may limit systemic side effects. CONCLUSION: Delivery of aerosolized-mAbs via the airways deserves further evaluation for treating lung cancers.


Assuntos
Anticorpos Monoclonais/administração & dosagem , Antineoplásicos/administração & dosagem , Neoplasias Pulmonares/tratamento farmacológico , Administração por Inalação , Aerossóis , Animais , Anticorpos Monoclonais/farmacocinética , Anticorpos Monoclonais/uso terapêutico , Anticorpos Monoclonais Humanizados , Antineoplásicos/farmacocinética , Antineoplásicos/uso terapêutico , Western Blotting , Linhagem Celular Tumoral , Cetuximab , Estabilidade de Medicamentos , Ensaio de Imunoadsorção Enzimática , Feminino , Injeções Intravenosas , Pulmão/efeitos dos fármacos , Pulmão/metabolismo , Pulmão/patologia , Neoplasias Pulmonares/metabolismo , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Distribuição Tecidual , Ensaios Antitumorais Modelo de Xenoenxerto
3.
Rev Prat ; 71(10): 1067-1071, 2021 12.
Artigo em Francês | MEDLINE | ID: mdl-35147358

RESUMO

Words from yesterday and today's pandemic: what medicine after covid? The covid-19 pandemic is a new phenomenon, unknown to our modern society, which has features in common with the plagues of history. We will try to answer two questions. Is the covid pandemic a crisis? How will the pandemic change our approach to health? The pandemic has generated a crisis, that is to say an event en¬dowed with a power of shock that goes beyond its integration into a causal series, an event with health, political, economic, and cultural consequences. To respond to this, our health establishments, our faculties, and all health players will have to work together to review their practices. Ethical choices will be necessary to find equitable solutions. These choices and actions have in common that they are conceived in an interdisciplinary reflection. We address some aspects: science and research, information and communica¬tion, ethics, health governance, patient participation.


Mots d'hier et pandémie d'aujourd'hui : quelle médecine après la crise du covid ? La pandémie de covid-19 est un phénomène nouveau pour notre société moderne mais qui possède des traits communs avec des fléaux de l'histoire. Cette pandémie est-elle une crise ? En quoi devrait-elle modifier notre approche de la santé ? La pandémie a généré une crise, c'est-à-dire un événement doté d'une puissance d'ébranlement qui dépasse son intégration dans une série causale, un événement aux conséquences sanitaires, politiques, économiques et culturelles. Pour la résoudre, nos éta¬blissements de santé, nos facultés, tous les acteurs de santé devront travailler ensemble et revoir leurs pratiques. Des choix éthiques s'imposeront pour trouver des solutions équitables. Ces choix et ces actions ont en commun de se concevoir dans une réflexion interdisciplinaire, dans les domaines tels que : science et recherche, information et communication, éthique, gouvernance sanitaire ou encore participation des patients.


Assuntos
COVID-19 , Medicina , Humanos , Pandemias , SARS-CoV-2
4.
Clin Chem ; 55(10): 1834-42, 2009 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-19661141

RESUMO

BACKGROUND: Tissue factor (TF), the main initiator of blood coagulation, is also a signaling protein that regulates cancer progression. TF synthesis was recently shown to be affected by tumor suppressor genes (TSGs) in tumor cell lines. We therefore studied TF gene (F3) expression and the status of genes coding for tumor protein p53 (TP53), phosphatase and tensin homolog (PTEN), and serine/threonine kinase 11 (STK11) in non-small cell lung cancer (NSCLC). Heparanase (HPSE) gene expression was also measured because this endo-beta-D-glucuronidase was recently shown to enhance TF gene expression. METHODS: TF and heparanase mRNA expression was measured by real-time PCR in 53 NSCLC tumors. Exons 5-8 of TP53 were sequenced from genomic DNA. Mutations of PTEN and STK11 were screened by multiplex ligation-dependent probe amplification. RESULTS: TF mRNA levels were significantly higher in T(3)-T(4) tumors (P = 0.04) and in stages III-IV of NSCLC (P = 0.03). Mutations of TP53, STK11, and PTEN were identified in 20 (37.7%), 21 (39%), and 20 (37.7%) of tumors, respectively. TF expression was higher in mutated TP53 (TP53(Mut)) (P = 0.02) and PTEN(Mut) (P = 0.03) samples. Moreover, TF mRNA increased from 2700 copies (no mutation) to 11 6415 when 3 TSG were mutated. Heparanase gene expression did not differ according to TF gene (F3) expression or TSG mutation. The median survival time was shorter in patients with tumor TF mRNA levels above median values (relative risk 2.2; P = 0.03, multivariate analysis) and when TP53 was mutated (relative risk 1.8; P = 0.02). CONCLUSIONS: These results provide clear evidence that combined oncogene events affecting TSG dramatically increase TF gene expression in lung tumors. Moreover, this study suggests that TF gene expression could be used as a prognostic marker in NSCLC.


Assuntos
Biomarcadores Tumorais/biossíntese , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Neoplasias Pulmonares/metabolismo , PTEN Fosfo-Hidrolase/genética , Tromboplastina/biossíntese , Proteína Supressora de Tumor p53/genética , Quinases Proteína-Quinases Ativadas por AMP , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Carcinoma Pulmonar de Células não Pequenas/patologia , Feminino , Glucuronidase/biossíntese , Humanos , Estimativa de Kaplan-Meier , Neoplasias Pulmonares/mortalidade , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Mutação , Reação em Cadeia da Polimerase , Modelos de Riscos Proporcionais , Proteínas Serina-Treonina Quinases/biossíntese , Taxa de Sobrevida
5.
Lung Cancer ; 58(1): 50-8, 2007 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-17624475

RESUMO

BACKGROUND: Lung cancer has the highest mortality-rate per cancer, with an overall 5-year survival <15%. Several non-randomized studies pointed out the high sensitivity of low dose computed tomography (LDCT) to detect early stage lung cancer. In France, Depiscan, a pilot RCT of LDCT versus chest X-ray (CXR), started on October 2002 to determine the feasibility of enrollment by general practitioners (GPs), investigations and diagnostic procedures by university hospital radiologists and multidisciplinary teams, data management by centralized clinical research assistants, and anticipate the future management of a large national trial. METHODS: GPs and occupational physicians (OPs) selected and enrolled 1000 subjects in 1 year. Eligible subjects were asymptomatic males or females aged 50-75 years with a current or former cigarette smoking history of >/=15 cigarettes per day for at least 20 years (former smokers having quit <15 years prior to enrollment). Based to randomization, annual LDCT or CXR screenings were planned at baseline and annually for 2 years. RESULTS: Between October 2002 and December 2004, 765 subjects were enrolled by 89 out of the 232 participating GPs and OPs. Complete clinical and imaging baseline data were available for 621 individuals out of the 765 enrolled, due to 144 noncompliant subjects who withdrew their consent. At least one nodule was detected in 152 out of 336 subjects (45.2%) in the LDCT screening, versus 21 out of 285 subjects (7.4%) in the CXR screening arm. Eight lung cancers were detected in the LDCT arm and one in the CXR arm. DISCUSSION: This pilot trial allows estimating that non-calcified nodules are 10 [6.36-17.07] times more often detected from LDCT than from CXR. However enrollment by GPs was more difficult than expected with 41% active investigators and a high rate (19%) of noncompliant patients. This experience speaks to the need for a high level of GPs formation and a large, coordinated clinical research team in such a trial. TRIAL REGISTRATION NUMBER: 02526.


Assuntos
Neoplasias Pulmonares/diagnóstico por imagem , Radiografia Pulmonar de Massa , Tomografia Computadorizada por Raios X , Idoso , Diagnóstico Precoce , Feminino , França , Humanos , Incidência , Neoplasias Pulmonares/patologia , Masculino , Programas de Rastreamento/métodos , Pessoa de Meia-Idade , Projetos Piloto , Prevalência , Fatores de Risco , Sensibilidade e Especificidade , Fumar
7.
Cancer Chemother Pharmacol ; 58(2): 237-44, 2006 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-16328414

RESUMO

AIM: To characterize gemcitabine aerosol, its in vitro activity against lung cancer cells, its deposition, and tolerance in a non-human primate model. METHODS: In vitro cytotoxicity of nebulized gemcitabine against NCI-H460 and A549 lung cancer cells was tested using a growth inhibition assay and compared with non-nebulized gemcitabine. The (99m)Tc-DTPA-radiolabeled gemcitabine aerosol was characterized by cascade impaction and the gemcitabine mass/(99m)Tc activity relationship was established for further quantitative nuclear imaging. Nine weekly inhalations at a target dose of 1 mg/kg body weight of gemcitabine were performed in three baboons using dynamic scintigraphic acquisitions for continuous monitoring of gemcitabine delivery during inhalation. Gemcitabine plasma concentrations were measured during the first inhalation. RESULTS: Growth inhibition assays for both NCI-H460 and A549 cells did not differ between nebulized and non-nebulized gemcitabine. Aerosol characterization showed a particle mass median aerodynamic diameter of 3.7+/-0.8 microm and a linear relationship between gemcitabine mass (y) and (99m)Tc activity (x) (y=0.82x - 10(-5), R (2)=0.88). No toxicity was observed after nine weekly inhalations of a mean dose of gemcitabine of 11.1 mg (88% of the target dose) as assessed from scintigraphic data. A dose-dependent peak plasma concentration of gemcitabine (20-74 ng/ml) was observed by the tenth minute of inhalation. CONCLUSIONS: We have characterized a gemcitabine aerosol suitable for intrathoracic airway deposition and demonstrated that jet nebulization does not alter the cytotoxic properties of the drug. In a primate model, we have developed a scintigraphic procedure for the monitoring of aerosol deposition, and we have demonstrated the safety of nine weekly aerosol administrations of gemcitabine.


Assuntos
Desoxicitidina/análogos & derivados , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Experimentais/tratamento farmacológico , Aerossóis , Animais , Desoxicitidina/administração & dosagem , Desoxicitidina/sangue , Desoxicitidina/uso terapêutico , Feminino , Neoplasias Pulmonares/diagnóstico por imagem , Modelos Animais , Neoplasias Experimentais/diagnóstico por imagem , Papio , Cintilografia , Gencitabina
9.
J Clin Oncol ; 20(1): 247-53, 2002 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-11773176

RESUMO

PURPOSE: To evaluate whether preoperative chemotherapy (PCT) could improve survival in resectable stage I (except T1N0), II, and IIIA non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS: A randomized trial compared PCT to primary surgery (PRS). PCT consisted of two cycles of mitomycin (6 mg/m(2), day 1), ifosfamide (1.5 g/m(2), days 1 to 3) and cisplatin (30 mg/m(2), days 1 to 3), and two additional postoperative cycles for responding patients. In both arms, patients with pT3 or pN2 disease received thoracic radiotherapy. RESULTS: Three hundred fifty-five eligible patients were randomized. Overall response to PCT was 64%. There were two preoperative toxic deaths. Postoperative mortality was 6.7% in the PCT arm and 4.5% in the PRS arm (P =.38). Median survival was 37 months (95% confidence interval [CI], 26.7 to 48.3) for PCT and 26.0 months (95% CI, 19.8 to 33.6) for PRS (P =.15). Survival differences between both arms increased from 3.8% (95% CI, 1.3% to 25.1%) at 1 year to 8.6% (95% CI, 2.64% to 24.4%) at 4 years. A quantitative interaction between N status and treatment was observed, with benefit confined to N0 to N1 disease (relative risk [RR], 0.68; 95% CI, 0.49 to 0.96; P =.027). After a nonsignificant excess of deaths during treatment, the effect of PCT was significantly favorable on survival (RR, 0.74; 95% CI, 0.56 to 0.99; P =.044). Disease-free survival time was significantly longer in the PCT arm (P =.033). CONCLUSION: Although impressive differences in median, 3-year, and 4-year survival were observed, they were not statistically significant, except for stage I and II disease.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/cirurgia , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/cirurgia , Adulto , Idoso , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Carcinoma Pulmonar de Células não Pequenas/patologia , Cisplatino/administração & dosagem , Terapia Combinada , Intervalo Livre de Doença , Feminino , Humanos , Ifosfamida/administração & dosagem , Neoplasias Pulmonares/mortalidade , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Mitomicina/administração & dosagem , Cuidados Pré-Operatórios , Modelos de Riscos Proporcionais , Taxa de Sobrevida
10.
Lung Cancer ; 47(3): 405-12, 2005 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-15713524

RESUMO

PURPOSE: This randomized phase II multicenter trial aimed at evaluating the efficacy and safety of the 4-week versus 3-week schedules of gemcitabine monotherapy in previously untreated elderly patients with advanced non-small cell lung cancer (NSCLC). PATIENTS AND METHODS: Chemonaive patients with stage IIIB or IV NSCLC, and age between 70 and 90 years, were randomized to receive gemcitabine dose of either 1000 mg/m2 on days 1, 8, 15, every 28 days (arm Q4W), or 1125 mg/m2 on days 1 and 8, every 21 days (arm Q3W). RESULTS: From June 1999 to January 2001, 81 patients (42 on arm Q4W; 39 on arm Q3W) were included. The median age was 75 on both arms; most patients (82.7%) were male, and had a Karnofsky performance status of 80 or 90 (76.5%). For arms Q4W and Q3W, respectively, the median time to treatment failure was 83 days (95% CI, 69-98 days) versus 92 days (95% CI, 63-113), and the median survival was 154 days (95% CI, 108-227) versus 205 days (95% CI, 125-344). The objective response rate was higher on arm Q3W (28.2%) than on arm Q4W (14.3%). Total number of cycles administered was 132 on arm Q4W (median 3, range 1-10 cycles) and 169 on arm Q3W (median 4, range 1-9 cycles). Patients on arm Q4W and Q3W, respectively, received 100.1 and 99.8% of the planned weekly mean dose. The most common grade, three to four toxicities, was neutropenia (17.1% on arm Q4W versus 18.9% on arm Q3W) and thrombocytopenia (12.2% on arm Q4W versus 2.6% on arm Q3W). CONCLUSION: Although both 3- and 4-week gemcitabine regimens were safely and effectively administered in chemonaive elderly patients with advanced NSCLC, the 3-week schedule appears to be the more convenient for this population. Moreover, even if this is only a phase II study this 3-week schedule appears to be at least as efficient as the 4-week regimen.


Assuntos
Antimetabólitos Antineoplásicos/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Desoxicitidina/análogos & derivados , Desoxicitidina/uso terapêutico , Neoplasias Pulmonares/tratamento farmacológico , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Antimetabólitos Antineoplásicos/administração & dosagem , Antimetabólitos Antineoplásicos/efeitos adversos , Carcinoma Pulmonar de Células não Pequenas/patologia , Desoxicitidina/administração & dosagem , Desoxicitidina/efeitos adversos , Esquema de Medicação , Feminino , Humanos , Neoplasias Pulmonares/patologia , Masculino , Resultado do Tratamento , Gencitabina
11.
J Aerosol Med ; 18(2): 198-206, 2005.
Artigo em Inglês | MEDLINE | ID: mdl-15966774

RESUMO

The purpose of this research was to evaluate the safety of pulmonary administration of gemcitabine and to determine the maximum tolerated dose by weekly pulmonary administrations in an animal model. Five groups of eight Wistar rats received gemcitabine at doses of 2, 4, 6, or 8 mg/kg or the vehicle solution by endotracheal spray with scintigraphic imaging of lung deposition. In order to document the safety of digestive exposure, five groups of eight rats received gemcitabine at the same dosages or the vehicle solution by gavage. Nine weekly sessions were planned, and blood cell counts and histological examinations were performed in live animals at day 64. Scintigraphic imaging confirmed pulmonary deposition in 310 of 316 spray administrations (98%) with homogeneous pattern of deposition. The maximum tolerated dose of gemcitabine by pulmonary administration was 4 mg/kg. At this dosage, administered once a week for 9 consecutive weeks, there were no chemotherapy-related deaths and no clinical, histological, or hematological signs of toxicity except for a decrease in platelet and red blood cell counts, with no clinical significance. The toxicity of gemcitabine was higher via oral than lung delivery in terms of weight loss and white blood cell toxicity at dosages of 2, 4, and 6 mg/kg. Pulmonary administration of gemcitabine is safe in rats at a maximum tolerated dose of 4 mg/kg once a week for 9 weeks. At an equivalent dosage, the toxicity of gemcitabine is lower by lung than oral administration.


Assuntos
Antimetabólitos Antineoplásicos/administração & dosagem , Desoxicitidina/análogos & derivados , Desoxicitidina/administração & dosagem , Sistemas de Liberação de Medicamentos , Pulmão/metabolismo , Administração por Inalação , Administração Oral , Animais , Estudos de Viabilidade , Feminino , Pulmão/diagnóstico por imagem , Dose Máxima Tolerável , Cintilografia , Ratos , Ratos Wistar , Gencitabina
12.
J Aerosol Med ; 17(1): 63-71, 2004.
Artigo em Inglês | MEDLINE | ID: mdl-15120014

RESUMO

The aim of this study was to assess a residual gravimetric method based on weighing dry filters to measure the aerosol output of nebulizers. This residual gravimetric method was compared to assay methods based on spectrophotometric measurement of terbutaline (Bricanyl, Astra Zeneca, France), high-performance liquid chromatography (HPLC) measurement of tobramycin (Tobi, Chiron, U.S.A.), and electrochemical measurements of NaF (as defined by the European standard). Two breath-enhanced jet nebulizers, one standard jet nebulizer, and one ultrasonic nebulizer were tested. Output produced by the residual gravimetric method was calculated by weighing the filters both before and after aerosol collection and by filter drying corrected by the proportion of drug contained in total solute mass. Output produced by the electrochemical, spectrophotometric, and HPLC methods was determined after assaying the drug extraction filter. The results demonstrated a strong correlation between the residual gravimetric method (x axis) and assay methods (y axis) in terms of drug mass output (y = 1.00 x -0.02, r(2) = 0.99, n = 27). We conclude that a residual gravimetric method based on dry filters, when validated for a particular agent, is an accurate way of measuring aerosol output.


Assuntos
Nebulizadores e Vaporizadores , Aerossóis/administração & dosagem , Antibacterianos/administração & dosagem , Broncodilatadores/administração & dosagem , Cromatografia Líquida de Alta Pressão , Filtração/instrumentação , Humanos , Espectrofotometria , Terbutalina/administração & dosagem , Tobramicina/administração & dosagem
13.
Bull Cancer ; 90(2): 151-66, 2003 Feb.
Artigo em Francês | MEDLINE | ID: mdl-12660134

RESUMO

CONTEXT: The "Standards, Options and Recommendations" (SOR) project, started in 1993, is a collaboration between the Federation of French Cancer Centers (FNCLCC), the 20 French cancer centers and specialists from French public university and general hospitals and private clinics. Its main objective is the development of clinical practice guidelines to improve the quality of health care and outcome for cancer patients. The methodology is based on literature review and critical appraisal by a multidisciplinary group of experts, with feedback from specialists in cancer care delivery. OBJECTIVES: To develop, according to the definitions of the Standards, Options and Recommendations, clinical practice guidelines for the management of non small cell lung carcinoma patients. METHODS: Data were identified by searching Medline and the personal reference lists of members of the expert groups, then submitted for review to independent reviewers. This is a short version of the SOR guideline covering diagnosis, treatment and follow-up and includes the algorithms for the management of patients with non-small cell lung cancer.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/terapia , Neoplasias Pulmonares/terapia , Algoritmos , Carcinoma Pulmonar de Células não Pequenas/diagnóstico , Endoscopia , Feminino , Humanos , Neoplasias Pulmonares/diagnóstico , Metástase Linfática , Masculino , Lesões Pré-Cancerosas/diagnóstico , Lesões Pré-Cancerosas/terapia
14.
Bull Cancer ; 89(10): 857-67, 2002 Oct.
Artigo em Francês | MEDLINE | ID: mdl-12441277

RESUMO

CONTEXT: The "Standards, Options and Recommendations" (SOR) project, started in 1993, is a collaboration between the Federation of French cancer centers (FNCLCC), the 20 French cancer centers, and specialists from French public universities, general hospitals and private clinics. The main objective is the development of clinical practice guidelines to improve the quality of health care and the outcome of cancer patients. The methodology is based on a literature review and critical appraisal by a multidisciplinary group of experts, with feedback from specialists in cancer care delivery. OBJECTIVES: To develop clinical practice guidelines for non small cell lung cancer patients according to the definitions of the Standards, Options and Recommendations project. METHODS: Data were identified by searching Medline , web sites, and using the personal reference lists of members of the expert groups. Once the guidelines were defined, the document was submitted for review to independent reviewers. RESULTS: This article presents the chapter "Prognosis significance of oncogenes and tumor suppressor genes" from the full report "Standards, Options and Recommendation for non small cell lung cancer" validated in August 2000. The main recommendations are: 1) No clear clinical prognostic value of oncogenes and tumor suppressor genes (p53, bcl-2, Ki-ras, c-erbB-2, Rb, p16) in non small cell lung cancer, can be established from the available evidences (standard, level of evidence C). 2) Prospective multicenter studies should be performed to assess prognostic significance of oncogenes and tumor suppressor genes in non small cell lung cancer.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/genética , Genes Supressores de Tumor , Neoplasias Pulmonares/genética , Mutação , Oncogenes , Inibidor p16 de Quinase Dependente de Ciclina/genética , Inibidor p16 de Quinase Dependente de Ciclina/metabolismo , França , Regulação Neoplásica da Expressão Gênica , Genes do Retinoblastoma , Genes erbB-2 , Genes p53 , Genes ras , Humanos , Prognóstico , Proteínas Proto-Oncogênicas c-bcl-2/genética , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo
15.
Bull Acad Natl Med ; 187(1): 153-60, 2003.
Artigo em Francês | MEDLINE | ID: mdl-14556461

RESUMO

Recent studies have benefited from the progress of the scanner in order to relaunch the debate on the opportunity of screening lung cancer. Even if these initial studies have succeeded in showing that the practise of helical scan allows the screening of a considerable proportion of cases at an early stage which may have 5-year survivals of up to 70%, there is no specific indication of the diminution of lung cancer-specific mortality. Studies of cohorts of several dozen millions subjects during a period of 8 to 10 years are to be realised and an international pool will be charged of the harmonization of the protocols in order to realize the analyse of the collected information. An experimental study of 1000 subjects financed by a grant have started recently in France.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/diagnóstico por imagem , Carcinoma Pulmonar de Células não Pequenas/prevenção & controle , Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias Pulmonares/prevenção & controle , Programas de Rastreamento , Radiografia Torácica , Tomografia Computadorizada Espiral , Idoso , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Ensaios Clínicos como Assunto , Estudos de Coortes , França , Humanos , Neoplasias Pulmonares/mortalidade , Programas de Rastreamento/economia , Pessoa de Meia-Idade , Projetos Piloto , Prevenção Primária , Radiografia Torácica/economia , Sensibilidade e Especificidade , Fumar/efeitos adversos , Fatores de Tempo , Tomografia Computadorizada Espiral/economia
17.
JPEN J Parenter Enteral Nutr ; 38(2): 196-204, 2014 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-24748626

RESUMO

BACKGROUND AND AIMS: The aim of this study was to evaluate on 1 day the prevalence of malnutrition in different types of cancer and the use of nutrition support in patients with cancer. METHODS: A 1-day prevalence survey was carried out in 154 French hospital wards. Malnutrition was defined as a body mass index (BMI) <18.5 in patients <75 years old or <21 in patients ≥75 years old and/or body weight loss >10% since disease onset. Oral food intake was measured using a visual analog scale. RESULTS: Nutrition status was collected for 1903 patients (1109 men and 794 women, 59.3 ± 13.2 years). Cancer was local in 25%, regional in 31%, and metastatic in 44% of patients. Performance status was 0 or 1 in 49.8%, 2 in 23.7%, 3 or 4 in 19.6% and not available in 6.5% of patients. Overall, 39% of patients were malnourished. The prevalence of malnutrition by disease site was as follows: head and neck, 48.9%; leukemia/lymphoma, 34.0%; lung, 45.3%; colon/rectum, 39.3%; esophagus and/or stomach, 60.2%; pancreas, 66.7%; breast, 20.5%; ovaries/uterus, 44.8%; and prostate, 13.9%. Regional cancer (odds ratio, 1.96; 95% confidence interval, 1.42-2.70), metastatic cancer (2.97; 2.14-4.12), previous chemotherapy (1.41; 1.05-1.89), and previous radiotherapy (1.53; 1.21-1.92) were associated with malnutrition. Only 28.4% of non-malnourished patients and 57.6% of malnourished patients received nutrition support. In all, 55% of patients stated that they were eating less than before the cancer, while 41.4% of patients stated that they had received nutrition counseling. CONCLUSIONS: The prevalence of malnutrition is high in patients with cancer, and systematic screening for and treatment of malnutrition is necessary.


Assuntos
Desnutrição/epidemiologia , Neoplasias/terapia , Apoio Nutricional/métodos , Idoso , Índice de Massa Corporal , Feminino , Seguimentos , Humanos , Modelos Logísticos , Masculino , Desnutrição/etiologia , Pessoa de Meia-Idade , Análise Multivariada , Neoplasias/complicações , Estado Nutricional , Apoio Nutricional/efeitos adversos , Prevalência , Estudos Prospectivos , Redução de Peso
18.
MAbs ; 6(6): 1638-48, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-25484066

RESUMO

K-ras mutations promote angiogenesis in lung cancer and contribute to the drug resistance of cancer cells. It is not clear whether K-ras mutated adenocarcinomas are sensitive to anti-angiogenic therapy with monoclonal antibodies (mAbs) that target vascular endothelial growth factor (VEGF). Anti-angiogenic mAbs are usually delivered systemically, but only a small proportion reaches the lung after intravenous injection. We investigated the relevance of a non-invasive pulmonary route for the delivery of anti-VEGF mAbs in the mouse K-ras(LA1) model. We found that pulmonary delivery of these mAbs significantly reduced the number of tumor lesions and inhibited malignant progression. The antitumor effect involves the VEGFR2-dependent inhibition of blood vessel growth, which impairs tumor proliferation. Pharmacokinetic analysis of aerosolized anti-VEGF showed its low rate of passage into the bloodstream, suggesting that this delivery route is associated with reduced systemic side effects. Our findings highlight the value of the aerosol route for administration of anti-angiogenic mAbs in pulmonary adenocarcinoma with K-ras activating-mutations.


Assuntos
Adenocarcinoma/tratamento farmacológico , Anticorpos Monoclonais/farmacologia , Neoplasias Pulmonares/tratamento farmacológico , Fator A de Crescimento do Endotélio Vascular/antagonistas & inibidores , Adenocarcinoma/genética , Adenocarcinoma/metabolismo , Aerossóis , Animais , Anticorpos Monoclonais/administração & dosagem , Anticorpos Monoclonais/farmacocinética , Anticorpos Neutralizantes/administração & dosagem , Anticorpos Neutralizantes/imunologia , Anticorpos Neutralizantes/farmacologia , Área Sob a Curva , Disponibilidade Biológica , Western Blotting , Proliferação de Células/efeitos dos fármacos , Células Cultivadas , Humanos , Imuno-Histoquímica , Injeções Intraperitoneais , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/metabolismo , Camundongos Endogâmicos C57BL , Camundongos Knockout , Mutação , Neovascularização Patológica/genética , Neovascularização Patológica/prevenção & controle , Proteínas Proto-Oncogênicas p21(ras)/genética , Resultado do Tratamento , Fator A de Crescimento do Endotélio Vascular/imunologia , Receptor 2 de Fatores de Crescimento do Endotélio Vascular/metabolismo
19.
Eur J Cancer ; 49(12): 2654-64, 2013 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-23735703

RESUMO

HYPOTHESIS: There will be a detectable increase in overall survival (OS) using preoperative (PRE) as opposed to perioperative (PERI) chemotherapy in resectable StageI-II non-small-cell lung cancer (NSCLC). METHODS: This multicenter, open-label, randomised trial with a 2×2 factorial design first compared two chemotherapy strategies (PRE versus PERI), then two chemotherapy regimens (gemcitabine-cisplatin [GP] versus paclitaxel-carboplatin [TC]). The PRE group received two preoperative cycles followed by two additional preoperative cycles, while the PERI group underwent two preoperative cycles followed by two postoperative cycles, the 3rd and 4th cycles being given only to responders in both cases. RESULTS: A total of 528 patients were randomised, 267 of which were assigned to the PRE group and 261 to the PERI group. Three-year OS did not differ between the two groups (67.4% and 67.7%, respectively; hazard ratio (HR)=1.01 [0.79-1.30], p=0.92), nor did 3-year disease-free survival, response rates, toxicity, or postoperative mortality. Pathological complete response was observed in 22 (8.2%) and 16 patients (6.1%), respectively. Although quality of life did not differ significantly, chemotherapy compliance was significantly higher in the PRE group. The proportion of responders who received Cycles 3 and 4 was significantly higher in the PRE group (90.4% versus 75.2%, p=0.001). In responders, the dose intensity of Cycles 3 and 4 was higher in the PRE group than in the PERI group (mean relative dose intensity of 90.4% versus 82.6%, respectively; p=0.0007). There was no difference between GP and TC in 3-year OS (HR=0.97 [95% confidence interval (CI): 0.76-1.25], p=0.80) or response rates. However, the regimens' toxicity profiles differed. CONCLUSIONS: This study failed to demonstrate any difference in survival between patients receiving preoperative and perioperative chemotherapy in early-stage NSCLC. The increase from two to four preoperative chemotherapy cycles did not increase the pathological response rate.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Neoplasias Pulmonares/tratamento farmacológico , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Carboplatina/administração & dosagem , Carboplatina/efeitos adversos , Carcinoma Pulmonar de Células não Pequenas/patologia , Carcinoma Pulmonar de Células não Pequenas/cirurgia , Cisplatino/administração & dosagem , Cisplatino/efeitos adversos , Terapia Combinada , Desoxicitidina/administração & dosagem , Desoxicitidina/efeitos adversos , Desoxicitidina/análogos & derivados , Intervalo Livre de Doença , Esquema de Medicação , Feminino , Humanos , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/cirurgia , Masculino , Pessoa de Meia-Idade , Náusea/induzido quimicamente , Estadiamento de Neoplasias , Neutropenia/induzido quimicamente , Paclitaxel/administração & dosagem , Paclitaxel/efeitos adversos , Assistência Perioperatória , Cuidados Pré-Operatórios , Qualidade de Vida , Resultado do Tratamento , Vômito/induzido quimicamente , Gencitabina
20.
Presse Med ; 41(3 Pt 1): e87-94, 2012 Mar.
Artigo em Francês | MEDLINE | ID: mdl-22079306

RESUMO

CONTEXT: The setting of multidisciplinary meeting (MDM) by the French Cancer Plan has introduced new decisional elements in the patient-physician relationship in oncology. METHODS: To assess the potential impact of MDM on this relationship, a study was conducted at the Tours Hospital: 145 questionnaires were collected from patients whose files have been discussed in MDM, 40 questionnaires were collected from physicians attending these meetings and an analysis of 324 files was performed. RESULTS: Patients recognize the decisional process of MDM as reassuring for 80% of them. However, a majority (73%) expressed that the most important for them is the relationship with the referring physician, almost all (96%) having a total or great confidence in him. The results emphasize that trust appears to be related to the quality of communication, open dialogue and the competence of the doctor in particular in the choice of treatment. A review of files shows that in 91% of cases, the opinion of the RCP is applied and that, in 69% of cases, the referring doctor delivers the information to the patient after MDM. From the physicians' perspective, 33/40 report that the MDM do not alter their relationship with the patient. We note that 35/40 express that the consultation after MDM facilitates the presentation of the decision and 37/40 that the decision is always or often applied in accordance with the opinion of the MDM. CONCLUSION: MDM appears in most cases in this study not to modify the patient-physician relationship. Due to the patient confidence into the referring physician, the role of this one is essential in integrating the decisional multidisciplinary opinion of MDM and it is important to ensure from his/her disengagement in the decisional process.


Assuntos
Tomada de Decisões , Gerenciamento Clínico , Oncologia , Equipe de Assistência ao Paciente , Relações Médico-Paciente , Comunicação , Humanos , Neoplasias/psicologia , Neoplasias/terapia , Participação do Paciente , Satisfação do Paciente , Encaminhamento e Consulta , Inquéritos e Questionários , Confiança
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