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1.
ESMO Open ; 9(2): 102236, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38350335

RESUMO

BACKGROUND: Sexual concerns are a major unaddressed need among survivors of breast cancer (BC) with significant negative effects on quality of life. We longitudinally analyzed sexual health over time, using patient-reported outcomes. METHODS: Patients with stage I-III BC prospectively included from the CANcer TOxicity cohort (CANTO) provided data at diagnosis, then 1, 2, and 4 years afterward. Sexual concerns outcomes included poor body image (score ≤91/100), poor sexual functioning (≤16/100), poor sexual enjoyment (≤66/100), and sexual inactivity (EORTC QLQ-B23). Multivariate generalized estimating equation models assessed associations with sexual concerns after diagnosis, adjusting for age, sociodemographic, tumor, treatment, and clinical characteristics. RESULTS: Nearly 78.1% among 7895 patients reported at least one sexual concern between diagnosis and 4 years' follow-up. Over time, the proportion of patients reporting sexual concerns either increased or remained constant with diagnosis. Less than half (46%, range 11.4-57) of the patients with sexual concerns reported the use of supportive care strategies, including gynecological or psychological consultations (range 11.4-57.4). Factors consistently associated with sexual concerns up to 4 years after diagnosis included already reporting the same concern at diagnosis [odds ratio (OR)poor body image 3.48 [95% confidence interval (CI) 3.11-3.89]; ORsexual inactivity 9.94 (95% CI 8.84-11.18), ORpoor sexual function 9.75 (95% CI 8.67-10.95), ORpoorsexual enjoyment 3.96 (95% CI 3.34-4.69)], endocrine therapy use [ORpoor body image 1.15 (95% CI 1.01-1.31); ORsexual inactivity 1.19 (95% CI 1.02-1.39), ORpoor sexual function 1.17 (95% CI 1.01-1.37), ORpoor sexual enjoyment 1.23 (95% CI 1.00-1.53)], and depression [ORpoor body image 2.00 (95% CI 1.72-2.34); ORsexual inactivity 1.66 (95% CI 1.40-1.97), ORpoor sexual function 1.69 (95% CI 1.43-2.00), ORpoor sexual enjoyment 1.94 (95% CI 1.50-2.51)]. Outcome-specific associations were also identified. CONCLUSIONS: Sexual concerns seem frequent, persistent, and insufficiently addressed. Pretreatment concerns, endocrine therapy, and emotional distress are commonly associated factors. A proactive evaluation of sexual health across the care continuum is needed, to promptly identify patients suitable for multidisciplinary counseling, referral, and supportive interventions.


Assuntos
Neoplasias da Mama , Saúde Sexual , Humanos , Feminino , Neoplasias da Mama/terapia , Neoplasias da Mama/psicologia , Qualidade de Vida , Sobreviventes/psicologia , Medidas de Resultados Relatados pelo Paciente
2.
Nat Chem ; 15(7): 1042, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-37407673
3.
ESMO Open ; 7(3): 100513, 2022 06.
Artigo em Inglês | MEDLINE | ID: mdl-35724624

RESUMO

BACKGROUND: Clinical trials allow development of innovative treatments and ameliorate the quality of clinical care in oncology. Data show that only a minority of patients are enrolled in clinical trials. We assessed enrolment in clinical trials and its correlates among women with early breast cancer. METHODS: We included 9516 patients with stage I-III breast cancer from the multicenter, prospective CANTO study (NCT01993498), followed-up until year 4 (Y4) post-diagnosis. We assessed factors associated with enrolment using multivariable logistic regression. In exploratory, propensity score matched analyses, we used multiple linear regression to evaluate the relationship of enrolment in clinical trials with the European Organisation for Research and Treatment of Cancer Quality Of Life (QoL) questionnaire (EORTC QLQ-C30) Summary Score and described clinical outcomes (distant disease event, invasive disease event, and death by any cause) according to enrolment. RESULTS: Overall, 1716 patients (18%) were enrolled in a clinical trial until Y4 post-diagnosis of breast cancer. Socioeconomic factors were not associated with enrolment. Centres of intermediate volume were most likely to enrol patients in clinical trials [versus low volume, odds ratio 1.45 (95% confidence interval (CI) 1.08-1.95), P = 0.0124]. Among 2118 propensity score matched patients, enrolment was associated with better QoL at Y4 (adjusted mean difference versus not enrolled 1.37, 95% CI 0.03-2.71, P = 0.0458), and clinical outcomes (enrolled versus not enrolled, distant disease event 7.3% versus 10.1%, P = 0.0206; invasive disease event 8.2% versus 10.5%, P = 0.0732; death by any cause 2.8% versus 3.7%, P = 0.2707). CONCLUSIONS: In this large study, one in five patients enrolled on a clinical trial until Y4 after diagnosis of early breast cancer. Geographical and centre-related factors were significantly associated with enrolment in clinical trials. Inclusion in clinical trials seemed associated with improved QoL and clinical outcomes. Access to innovation for early-stage breast cancer patients should be encouraged and facilitated by overcoming organizational and geographical barriers to recruitment.


Assuntos
Neoplasias da Mama , Neoplasias da Mama/terapia , Feminino , Humanos , Estudos Prospectivos , Qualidade de Vida , Inquéritos e Questionários
4.
J Appl Anim Welf Sci ; 25(3): 287-296, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-34056962

RESUMO

Functional analysis (FA) is a method developed and used by behavior analysts in human clinical settings to identify possible environmental variables that reinforce undesired behavior. FA is increasingly being applied to better understand the behavior of nonhuman animals. When training monkeys in a room with others, disruptive behavior displayed by neighboring monkeys can impede training progress. In the present study, a FA identified possible reinforcers of disruptive behavior (loud shaking of a toy) exhibited frequently (24% duration pre-treatment) by a rhesus macaque (Macaca mulatta) during in-room training sessions. The functional analysis identified that contingent delivery of foods was maintaining the disruptive behavior, with a mean percent duration of 57% in this condition. The implementation of a function-based treatment consisting of continuous access to a preferred food during in-room training sessions successfully decreased disruptive behavior by over 90% as measured during 15 subsequent sessions. This study advances the current literature applying functional analysis to nonhuman primates as a means of determining the reinforcers maintaining aberrant or undesirable behavior and applying effective treatments based on understanding this function.


Assuntos
Comportamento Problema , Animais , Humanos , Macaca mulatta , Projetos de Pesquisa
5.
Dalton Trans ; 50(37): 12843-12849, 2021 Sep 28.
Artigo em Inglês | MEDLINE | ID: mdl-34473174

RESUMO

Extensive DFT calculations with several exchange-correlation functionals indicate that molybdenum-dichlorido Viking helmet corroles are noninnocent with significant MoIV-corrole˙2- character. The effect is mediated by a Mo(4d)-corrole(π) orbital interaction similar to that postulated for MnCl, FeCl and FeNO corroles. The effect also appears to operate in tungsten-dichlorido corroles but is weaker relative to that for Mo. In contrast, MoO triarylcorroles do not exhibit a significant degree of corrole radical character. Furthermore, the Soret absorption maxima of a series of MoCl2 tris(para-X-phenyl)corrole derivatives were found to redshift dramatically with increasing electron-donating character of the para substituent X, essentially clinching the case for a noninnocent macrocycle in MoCl2 corroles.

6.
Naturwissenschaften ; 108(4): 25, 2021 Jun 06.
Artigo em Inglês | MEDLINE | ID: mdl-34091791

RESUMO

Deception has evolved in a range of taxa. When deception imposes costs, yet persists over generations, exploited species typically have traits to help them bear or minimise costs. The sexually deceptive orchids, Cryptostylis spp., are pollinated by tricking male haplodiploid wasps (Lissopimpla excelsa) into mating with flowers, which offer no reward and often elicit sperm wastage. We hypothesise that by attracting haplodiploid species, orchids have a pollinator ideally suited to withstand the costs of sexual deception-and a selective advantage compared to other orchids. Haplodiploid females can reproduce with or without sperm-albeit when spermless, females can only have sons. Through orchid deception and sperm wastage, deceived haplodiploid populations could become male biased, providing enough males to share between orchids and females. In this way, pollinator populations can persist despite high densities of sexually deceptive orchids. Here, we aim to broadly test this prediction using museum and digital records of the pollinator, L. excelsa, from sites with or without orchids. For robustness, we also analyse the sex ratio of a sister ichneumonid species that occurs in the same areas but is not deceived by orchids. We found that at sites with orchids, L. excelsa was significantly more male biased than at sites without orchids and significantly more male biased than the sister ichneumonid. This survey is the first to test the population-level effects of sexually deceptive orchids on their pollinator. It supports our prediction that orchid deception can drive male-biased sex ratios in exploited pollinators.


Assuntos
Flores/anatomia & histologia , Flores/fisiologia , Orchidaceae/anatomia & histologia , Orchidaceae/fisiologia , Polinização/fisiologia , Animais , Feminino , Masculino , Museus , Comportamento Sexual Animal/fisiologia
7.
Neurologia (Engl Ed) ; 35(8): 563-567, 2020 Oct.
Artigo em Inglês, Espanhol | MEDLINE | ID: mdl-29291907

RESUMO

INTRODUCTION: The diagnosis of vascular parkinsonism (VP) is based on a series of clinical criteria and neuroimaging findings. An increase in transcranial Doppler ultrasonography pulsatility index (PI) has been described as a frequent finding in patients with VP. We aimed to confirm this association and to determine the PI value with the highest sensitivity and specificity for diagnosis of VP. METHOD: PI was determined in all patients admitted to Hospital Universitari i Politècnic La Fe due to parkinsonism between January 2012 and June 2016. We assessed the probability of having VP based on PI values in patients with a definite diagnosis of either VP or idiopathic Parkinson's disease (IPD). A ROC curve was created to determine the PI value with the highest sensitivity and specificity. RESULTS: We assessed a total of 146 patients with suspected parkinsonism; 54 (37%) were diagnosed with IPD and 15 (10%) with VP. Patients with VP were significantly older than those with IPD (mean age of 79 vs 68.5, P=.00144) and had a higher PI (median of 1.29 [IQR: 1.09-1.38] vs 0.96 [IQR: 0.89-1.16], P=.01328). In our sample, a PI of 1.09 conferred 84% sensitivity and 70% specificity. CONCLUSIONS: In our series, the PI was significantly higher in patients with VP than in those with IPD. We therefore support the use of transcranial Doppler ultrasonography for the initial assessment of elderly patients with akinetic-rigid syndrome.


Assuntos
Doença de Parkinson Secundária/diagnóstico , Doença de Parkinson/diagnóstico , Ultrassonografia Doppler Transcraniana/métodos , Idoso , Idoso de 80 Anos ou mais , Diagnóstico Diferencial , Feminino , Humanos , Masculino , Neuroimagem , Doenças Vasculares
8.
Artigo em Inglês, Espanhol | MEDLINE | ID: mdl-30528059

RESUMO

OBJECTIVE: Surgical site infections (SSIs) are complications that predispose to a high risk of unfavourable surgical outcomes. The aim of this study was to assess the SSI rate in this type of patients and their prognosis with similar treatment. MATERIALS AND METHODS: A retrospective case series of 799 patients above 18 years old with spinal instrumentation surgery, between January 2010 and December 2014 in the traumatology and orthopaedic surgery department of our institution. All patients with SSIs were treated by debridement, graft replacement, retention of the instrumentation and lengthy courses of antimicrobial therapy. The patients were followed up for a period of 12 months. RESULTS: Of all the patients with arthrodesis, 32 (4%) had spinal SSIs. Three patients were lost to follow-up. The final sample analyzed comprised 29 cases, with a median age of 54.9 years (IQR, 45.7-67 years) and a Charlson comorbidity index of 2.0 (IQR; 0-3). A microbiological diagnosis was obtained in 75.8% of the cases. Of these, the ISSs were monomicrobial in 68.2% and polymicrobial in 31.8%. Once treatment had been completed, 96% were cured without sequelae, and the rate of recurrence and reoperation was 4%. CONCLUSIONS: Treatment based on debridement, retention of the instrumentation, graft replacement and lengthy courses of antimicrobial therapy seems a very effective strategy in the treatment of patients with deep surgical site infection in spine surgery.


Assuntos
Infecções por Bactérias Gram-Negativas/diagnóstico , Infecções por Bactérias Gram-Negativas/terapia , Infecções por Bactérias Gram-Positivas/diagnóstico , Infecções por Bactérias Gram-Positivas/terapia , Fusão Vertebral , Infecção da Ferida Cirúrgica/diagnóstico , Infecção da Ferida Cirúrgica/terapia , Adolescente , Adulto , Idoso , Antibacterianos/uso terapêutico , Transplante Ósseo , Terapia Combinada , Desbridamento , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Reoperação/instrumentação , Reoperação/métodos , Estudos Retrospectivos , Fusão Vertebral/instrumentação , Adulto Jovem
9.
Eur J Cancer ; 87: 140-146, 2017 12.
Artigo em Inglês | MEDLINE | ID: mdl-29149760

RESUMO

BACKGROUND: The GETUG 13 phase III trial tested personalised chemotherapy based on tumour marker decline in patients with poor-prognosis germ-cell tumour (GCT) and demonstrated that a dose-dense regimen improves progression-free survival in patients with an unfavourable decline. We investigated the pattern of relapse for patients included in GETUG 13. METHODS: We conducted an analysis of relapse events in patients from GETUG 13. Baseline procedures before inclusion in the trial comprised a thoraco-abdomino-pelvic computed tomography scan and a magnetic resonance imaging of the brain. RESULTS: With a median follow-up of 4.1 years (0.3; 8.8 years), a progression event was observed in 109/254 patients (43%). First event consisted in a marker progression only in 47 patients (43%), a radiographic progression only in 35 patients (32%), a mix progression on both markers and imaging in 12 patients (11%) and death in 15 patients (14%). In patients with radiographic progression only, brain was the predominant site (n = 19/35, 54%). Among patients with unfavourable decline who experienced a radiographic progression (as first and subsequent progression event, n = 58), brain was a site of progression in 28 patients (48%): 12/30 (40%) in patients treated with cisplatin, bleomycin and etoposide and 16/28 (57%) in those treated with dose-dense chemotherapy. CONCLUSIONS: Brain metastases develop often, early and frequently as the only site of relapse in the course of poor-prognosis GCT. This raises the question of early detection and optimal treatment of brain metastases in these patients, e.g. by integrating a systematic brain MRI after 2-3 months of chemotherapy.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Encefálicas/secundário , Neoplasias Embrionárias de Células Germinativas/tratamento farmacológico , Neoplasias Embrionárias de Células Germinativas/secundário , Neoplasias Testiculares/tratamento farmacológico , Neoplasias Testiculares/patologia , Neoplasias Encefálicas/diagnóstico por imagem , Neoplasias Encefálicas/mortalidade , Ensaios Clínicos Fase III como Assunto , Progressão da Doença , Intervalo Livre de Doença , França , Humanos , Estimativa de Kaplan-Meier , Imageamento por Ressonância Magnética , Masculino , Estudos Multicêntricos como Assunto , Neoplasias Embrionárias de Células Germinativas/diagnóstico por imagem , Neoplasias Embrionárias de Células Germinativas/mortalidade , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Fatores de Risco , Neoplasias Testiculares/diagnóstico por imagem , Neoplasias Testiculares/mortalidade , Fatores de Tempo , Tomografia Computadorizada por Raios X , Resultado do Tratamento , Estados Unidos
10.
Ann Oncol ; 26(8): 1692-7, 2015 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-25943350

RESUMO

BACKGROUND: Inflammatory breast cancer (IBC) is a rare and aggressive disease requiring a multimodal treatment. We evaluated the benefit of adding docetaxel-5-fluorouracil (D-5FU) regimen after preoperative dose-intense (DI) epirubicin-cyclophosphamide (EC) and locoregional treatment in IBC patients. PATIENTS AND METHODS: PEGASE 07 was a national randomized phase III open-label study involving 14 hospitals in France. Women with nonmetastatic IBC were eligible and randomly assigned to receive either four cycles of DI EC (E 150 mg/m(2) and C 4000 mg/m(2) every 3 weeks with repeated hematopoietic stem cell support), then mastectomy with axillary lymph node dissection, and radiotherapy (arm A) or the same treatment followed by four cycles of D-5FU (D 85 mg/m(2), day 1 and 5FU 750 mg/m(2)/day continuous infusion, days 1-5 every 3 weeks) administered postradiotherapy (arm B). Patients with hormone receptor-positive tumors received hormonal therapy. Disease-free survival (DFS) was the primary end point. Secondary end points included tolerance, pathological complete response (pCR) rate, and overall survival (OS). RESULTS: Between January 2001 and May 2005, 174 patients were enrolled and treated (87 in each arm). Median follow-up was similar in both arms: 59.6 months [95% confidence interval (CI) 58.4-60.3] in arm A and 60.5 months (95% CI 58.3-61.4) in arm B. The estimated 5-year DFS rates were not different: 55% (95% CI 43.9-64.7) in arm A and 55.5% (95% CI 44.3-65.3) in arm B [hazard ratio (HR) = 0.94 (0.61-1.48); P = 0.81]. Identical results were observed for 5-year OS: 70.2% (95% CI 59.1-78.8) in arm A and 70% (95% CI 58.8-78.7) in arm B [HR = 0.93 (0.55-1.60); P = 0.814]. Following DI EC induction, in-breast and global (breast plus nodes) pCR were 28.9% and 20.1%, respectively. Estrogen receptor and pCR status were independently associated with survival. CONCLUSION: The addition of D-5FU after preoperative DI EC and standard local therapy did not improve DFS in IBC. CLINICAL TRIAL NUMBER: ClinicalTrials.gov identifier: NCT02324088.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma Ductal de Mama/tratamento farmacológico , Carcinoma Lobular/tratamento farmacológico , Neoplasias Inflamatórias Mamárias/tratamento farmacológico , Mastectomia , Terapia Neoadjuvante/métodos , Adulto , Antineoplásicos Hormonais/administração & dosagem , Axila , Quimiorradioterapia Adjuvante/métodos , Quimioterapia Adjuvante/métodos , Ciclofosfamida/administração & dosagem , Intervalo Livre de Doença , Docetaxel , Epirubicina/administração & dosagem , Feminino , Fluoruracila/administração & dosagem , Humanos , Neoplasias Inflamatórias Mamárias/metabolismo , Excisão de Linfonodo , Pessoa de Meia-Idade , Receptor ErbB-2/metabolismo , Receptores de Estrogênio/metabolismo , Receptores de Progesterona/metabolismo , Taxoides/administração & dosagem
11.
Mult Scler Int ; 2014: 975803, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-24795824

RESUMO

Objectives. To examine relationships between conventional MRI measures and the paced auditory serial addition test (PASAT) and symbol digit modalities test (SDMT). Methods. A systematic literature review was conducted. Included studies had ≥30 multiple sclerosis (MS) patients, administered the SDMT or PASAT, and measured T2LV or brain atrophy. Meta-analysis of MRI/information processing speed (IPS) correlations, analysis of MRI/IPS significance tests to account for reporting bias, and binomial testing to detect trends when comparing correlation strengths of SDMT versus PASAT and T2LV versus atrophy were conducted. Results. The 39 studies identified frequently reported only significant correlations, suggesting reporting bias. Direct meta-analysis was only feasible for correlations between SDMT and T2LV (r = -0.45, P < 0.001) and atrophy in patients with mixed-MS subtypes (r = -0.54, P < 0.001). Familywise Holm-Bonferroni testing found that selective reporting was not the source of at least half of significant results reported. Binomial tests (P = 0.006) favored SDMT over PASAT in strength of MRI correlations. Conclusions. A moderate-to-strong correlation exists between impaired IPS and MRI in mixed MS populations. Correlations with MRI were stronger for SDMT than for PASAT. Neither heterogeneity among populations nor reporting bias appeared to be responsible for these findings.

12.
Ann Oncol ; 24(3): 625-32, 2013 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-23117074

RESUMO

Background The genomic grade index (GGI) completes the prognostic value of histological grade (HG). Other proliferation markers include the mitotic activity index (MAI) and the Ki67 immunohistochemistry (IHC) status. We compared the prognostic value of GGI, HG, MAI, Ki67 IHC and messenger RNA (mRNA) status in node-positive breast cancer (BC) patients treated with adjuvant anthracycline-based chemotherapy in the prospective PACS01 trial. Patients and methods The five proliferation-related parameters (GGI, Ki67 mRNA expression and centrally determined HG, MAI, and Ki67 IHC status) of tumours were available for 204 cases and analysed as continuous values. We compared the correlations of each one with the other proliferation-related parameters and with histoclinical variables including the disease-free survival (DFS). Results Expected correlations were observed between the five parameters and for each parameter with biological features (hormone-receptor and HER2 status, molecular subtypes), but the GGI displayed the strongest correlations. The GGI outperformed the prognostic performance of the four other proliferation-related parameters for the DFS in all 204 patients and in the 95 HG2 patients. In multivariate analysis including the classical prognostic factors, only GGI remained significant. Finally, the GGI outperformed the prognostic performance of MKI67 mRNA expression in a series of 1599 samples and 656 HG2 cases. Conclusions In this small pilot biomarker study ancillary to the PACS01 trial, the GGI outperforms the prognostic performance of centrally determined HG, MAI, Ki67 IHC status and mRNA expression. Further validation is warranted in larger series.


Assuntos
Biomarcadores Tumorais/metabolismo , Neoplasias da Mama/patologia , Carcinoma Ductal de Mama/patologia , Antígeno Ki-67/metabolismo , Índice Mitótico , Neoplasias da Mama/genética , Neoplasias da Mama/mortalidade , Carcinoma Ductal de Mama/genética , Carcinoma Ductal de Mama/mortalidade , Ensaios Clínicos Fase III como Assunto , Intervalo Livre de Doença , Feminino , Humanos , Imuno-Histoquímica , Metástase Linfática , Pessoa de Meia-Idade , Análise Multivariada , Gradação de Tumores , Prognóstico , Modelos de Riscos Proporcionais , Curva ROC , Estudos Retrospectivos
13.
Oncogene ; 31(9): 1196-206, 2012 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-21785460

RESUMO

The current histoclinical breast cancer classification is simple but imprecise. Several molecular classifications of breast cancers based on expression profiling have been proposed as alternatives. However, their reliability and clinical utility have been repeatedly questioned, notably because most of them were derived from relatively small initial patient populations. We analyzed the transcriptomes of 537 breast tumors using three unsupervised classification methods. A core subset of 355 tumors was assigned to six clusters by all three methods. These six subgroups overlapped with previously defined molecular classes of breast cancer, but also showed important differences, notably the absence of an ERBB2 subgroup and the division of the large luminal ER+ group into four subgroups, two of them being highly proliferative. Of the six subgroups, four were ER+/PR+/AR+, one was ER-/PR-/AR+ and one was triple negative (AR-/ER-/PR-). ERBB2-amplified tumors were split between the ER-/PR-/AR+ subgroup and the highly proliferative ER+ LumC subgroup. Importantly, each of these six molecular subgroups showed specific copy-number alterations. Gene expression changes were correlated to specific signaling pathways. Each of these six subgroups showed very significant differences in tumor grade, metastatic sites, relapse-free survival or response to chemotherapy. All these findings were validated on large external datasets including more than 3000 tumors. Our data thus indicate that these six molecular subgroups represent well-defined clinico-biological entities of breast cancer. Their identification should facilitate the detection of novel prognostic factors or therapeutical targets in breast cancer.


Assuntos
Neoplasias da Mama/classificação , Biomarcadores Tumorais/genética , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/genética , Neoplasias da Mama/mortalidade , Análise por Conglomerados , Bases de Dados Genéticas , Feminino , Perfilação da Expressão Gênica , Humanos , Prognóstico , Reprodutibilidade dos Testes , Transdução de Sinais , Análise de Sobrevida , Transcriptoma , Resultado do Tratamento
14.
Br J Cancer ; 105(10): 1480-6, 2011 Nov 08.
Artigo em Inglês | MEDLINE | ID: mdl-22009030

RESUMO

BACKGROUND: A dose-dense strategy has been considered to improve results of adjuvant chemotherapy for breast cancer. This randomised phase II trial investigated the feasibility of this approach with sequential anthracyclines and taxanes-based chemotherapy. METHODS: Patients with high-risk node-positive breast cancer were treated with three cycles of fluorouracil 500 mg m(-2), epirubicin 100 mg m(-2), cyclophosphamide 500 mg m(-2) (FEC 100) followed by three cycles of docetaxel 100 mg m(-2) delivered at 2-weekly intervals supported by primary prophylaxis with filgrastim. All patients were randomised to either uninterrupted treatment (arm A) or to have a 2-week additional period of rest between the FEC and docetaxel (arm B). The primary endpoint was the rate of success of chemotherapy delivery. Using a two-stage Fleming design, 120 patients were required with one interim analysis. RESULTS: In March 2005, enrolment was stopped into arm A after the observation of severe skin toxicities. Following the planned interim analysis, the study was closed because of the high rate of grade 3/4 skin toxicities in both arms (arm A: 32.4% and arm B: 18.9%). CONCLUSION: Sequential dose-dense FEC 100 followed by docetaxel 100 mg m(-2) is not feasible. Feasibility still depends largely on several factors including the choice of drugs, dosage and sequence of administration.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Neoplasias da Mama/tratamento farmacológico , Quimioterapia Adjuvante , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Ciclofosfamida/administração & dosagem , Ciclofosfamida/efeitos adversos , Relação Dose-Resposta a Droga , Epirubicina/administração & dosagem , Epirubicina/efeitos adversos , Feminino , Fluoruracila/administração & dosagem , Fluoruracila/efeitos adversos , Humanos , Pessoa de Meia-Idade
15.
Br J Pharmacol ; 164(8): 2003-14, 2011 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-21649641

RESUMO

BACKGROUND AND PURPOSE: Expression of inducible NOS (iNOS) is important in certain inflammatory diseases. We determined if the hormone aldosterone, a mineralocorticoid receptor (MR) agonist, affects LPS activation of iNOS expression in rat aortic smooth muscle cells (RASMC). EXPERIMENTAL APPROACH: Cultured RASMC were treated with LPS, with or without agonists/antagonists of steroid receptors. iNOS expression was determined by nitrite assays on culture medium removed from treated cells and by immunoblotting of cell protein extracts. KEY RESULTS: LPS (1 µg·mL(-1) ) increased nitrite and iNOS protein above that in control (untreated) cells. These effects of LPS were reduced by aldosterone (0.1-10 µM). The MR antagonists, eplerenone (10 µM) and spironolactone (10 or 50 µM), did not inhibit these actions of 1 µM aldosterone, but the latter were prevented by 10 µM mifepristone, a glucocorticoid (GR) and progestogen receptor (PR) antagonist. Mifepristone also prevented the reduction of LPS-induced nitrite increase produced by 1 µM dexamethasone (GR agonist) and 10 µM progesterone (PR agonist). Spironolactone (10-50 µM) by itself decreased LPS-induced increases in nitrite and iNOS protein. Mifepristone (10 µM) partially reversed these effects of 10 µM spironolactone, but not those of 50 µM; the effects of 50 µM spironolactone were also unchanged when mifepristone was increased to 50 µM. CONCLUSIONS AND IMPLICATIONS: This pharmacological profile suggests that aldosterone, and possibly 10 µM spironolactone, use mechanisms that are dependent on PR and/or GR, but not MR, to inhibit iNOS induction in RASMC. With 50 µM spironolactone, other inhibitory mechanisms requiring further investigation may become predominant.


Assuntos
Aldosterona/farmacologia , Aorta Torácica/efeitos dos fármacos , Lipopolissacarídeos/farmacologia , Músculo Liso Vascular/efeitos dos fármacos , Óxido Nítrico Sintase Tipo II/metabolismo , Esteroides/farmacologia , Animais , Aorta Torácica/citologia , Aorta Torácica/enzimologia , Células Cultivadas , Eplerenona , Masculino , Mifepristona/farmacologia , Músculo Liso Vascular/citologia , Músculo Liso Vascular/enzimologia , Óxido Nítrico Sintase Tipo II/biossíntese , Ratos , Ratos Sprague-Dawley , Espironolactona/análogos & derivados , Espironolactona/farmacologia
17.
Br J Cancer ; 102(7): 1081-4, 2010 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-20197767

RESUMO

BACKGROUND: Participants are showing great interest these days in obtaining the results of clinical trials. The aim of this study was to assess patients' uptake and understanding of the results of the trial in which they have participated and the impact of a letter offering patients the possibility of consulting the trial results on a specific website. METHODS: Breast cancer patients participating in a trial on the efficacy of Trastuzumab were randomly subdivided into an Internet group (who received the letter of invitation) and a control group (who did not receive it). Among 115 HER2-positive women from 21 centres, 107 (93%) answered a self-administered questionnaire. RESULTS: Most of the patients in both groups had access to the Internet (72.0%). The majority (97.2%) stated that receiving information about the trial results would be useful, and the oncologist was the most frequently preferred information provider. The Internet group's declared uptake of the trial results was only slightly higher (47.1% vs 33.9%; P=0.166); however, they understood the results significantly more accurately (18.8% vs 5.6%; P=0.039). INTERPRETATION: Although Internet was not the respondents' preferred source of information, the possibility of using this source slightly increased the uptake and understanding of the results.


Assuntos
Compreensão , Disseminação de Informação/métodos , Ensaios Clínicos Controlados Aleatórios como Assunto , Idoso , Neoplasias da Mama/tratamento farmacológico , Correspondência como Assunto , Feminino , Humanos , Internet , Pessoa de Meia-Idade , Educação de Pacientes como Assunto , Participação do Paciente , Preferência do Paciente
18.
Ann Oncol ; 21(7): 1448-1454, 2010 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-20038515

RESUMO

BACKGROUND: Using data from the PACS 01 randomized trial, we evaluated the cost-effectiveness of anthracyclines plus docetaxel (Taxotere; FEC-D) versus anthracyclines alone (FEC100) in patients with node-positive breast cancer. PATIENTS AND METHODS: Costs and outcomes were assessed in 1996 patients and the incremental cost-effectiveness ratios (ICERs) were estimated, using quality-adjusted life years (QALYs) as outcome. To deal with uncertainty due to sampling fluctuations, confidence regions around the ICERs were calculated and cost-effectiveness acceptability curves were drawn up. Sensitivity analyses were also carried out to assess the robustness of conclusions. RESULTS: The mean cost of treatment was 33% higher with strategy FEC-D, but this difference decreased to 18% at a 5-year horizon. The ICER of FEC-D versus FEC100 was estimated to be 9665euro per QALY gained (95% confidence interval euro2372-euro55 515). The estimated probability that FEC-D was cost-effective reached >96% for a threshold of euro50 000 per QALY gained. If the price of taxane decreased slightly, the ICER would reach some very reasonable levels and this strategy would therefore be much more cost-effective. CONCLUSION: The sequential use of FEC100 followed by docetaxel appears to be a cost-effective alternative, even when uncertainty is taken into account.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/economia , Linfonodos/patologia , Adulto , Idoso , Antraciclinas/administração & dosagem , Neoplasias da Mama/patologia , Quimioterapia Adjuvante , Análise Custo-Benefício , Docetaxel , Feminino , Humanos , Pessoa de Meia-Idade , Modelos Econômicos , Metástase Neoplásica , Estadiamento de Neoplasias , Anos de Vida Ajustados por Qualidade de Vida , Taxa de Sobrevida , Taxoides/administração & dosagem , Resultado do Tratamento
19.
AJNR Am J Neuroradiol ; 29(8): 1601-2, 2008 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-18499794

RESUMO

We report the case of a child with multiple pituitary hormone deficiencies and a truncated pituitary stalk on MR imaging who had recovery of normal secretion of pituitary hormones in early adulthood. Follow-up MR imaging examination after recovery revealed marked enlargement of the proximal pituitary stalk. The case of our patient helps to explain the mechanism whereby some patients experience recovery of hormonal function.


Assuntos
Nanismo Hipofisário/patologia , Hormônio do Crescimento Humano/deficiência , Hipopituitarismo/patologia , Adeno-Hipófise/anormalidades , Adeno-Hipófise/patologia , Pré-Escolar , Humanos , Masculino , Síndrome
20.
Vet Dermatol ; 18(6): 401-11, 2007 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-17991157

RESUMO

Ferrets are important companion animals that incur a multitude of cutaneous diseases requiring diagnostic dermatohistopathology. This study provides a description of the histology of normal ferret skin, emphasizing changes in the interval from preweaning to adulthood, an essential basis for identification of pathological situations. Skin samples obtained post-mortem from 29 topographical sites on 41 ferrets, revealed in the haired, general body surface skin an epidermis consisting of strata basale, spinosum, granulosum, and corneum and a dermis consisting of strata papillare and reticulare. Adult skin contained compound hair follicles composed of one primary hair and a collection of secondary hairs with a primary to secondary ratio of 1/5-1/15. All hairs emerged through the same follicle outlet of the skin surface. There was associated with each primary follicle, an arrector pili muscle, a multilobular sebaceous gland, and a coiled tubular sweat gland, but secondary hairs lacked these features. Compound follicles, grouped mainly as triads across the body surface, were already fully formed in the youngest group studied (3 to 6 weeks). The secondary hairs all developed from one specific region of the primary follicles and smaller ones were formed with increasing age. The differences found in specialized body regions are described. Demodex sp. mites were found in follicles and sebaceous glands in nine of 25 individuals in the perianal, vulvar, preputial, facial, and caudal abdominal skin.


Assuntos
Furões , Folículo Piloso/anatomia & histologia , Pele/anatomia & histologia , Envelhecimento , Animais , Animais Recém-Nascidos/anatomia & histologia , Feminino , Folículo Piloso/ultraestrutura , Masculino , Pele/ultraestrutura
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