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1.
Prog Urol ; 33(6): 307-318, 2023 May.
Artigo em Inglês | MEDLINE | ID: mdl-37088584

RESUMO

INTRODUCTION: Currently, bladder cancer detection is based on cytology and cystoscopy. White light cystoscopy (WLC) is an invasive procedure and may under-detect flat lesions. Blue light cystoscopy (BLC) and narrow band imaging (NBI) cystoscopy are new modalities that could improve the detection of non-muscle invasive bladder cancer (NMIBC) and its recurrence or progression to muscle invasive bladder cancer. We present a systematic review on BLC and NBI cystoscopy for bladder cancer diagnosis and NMIBC follow-up. MATERIAL AND METHODS: All available systematic reviews and meta-analyses on cystoscopy published in PubMed® between May 2010 and March 2021 were identified and reviewed. The main endpoints were clinical performance for bladder cancer diagnosis and for recurrence or progression detection during NMIBC follow-up, and additional value compared with cytology and/or WLC. RESULTS: Most of the meta-analyses and systematic reviews published suggest a better sensitivity of BLC and NBI cystoscopy compared to WLC, particularly for the detection of flat lesions (CIS). NBI- and BLC-guided TURBT could decrease the recurrence rates. However, their clinical utility to reduce progression rate and increase survival is still unclear. CONCLUSIONS: BLC and NBI cystoscopy are efficient techniques for bladder cancer diagnosis and NMIBC follow-up. However, their clinical benefit remains to be confirmed.


Assuntos
Cistoscopia , Neoplasias da Bexiga Urinária , Humanos , Cistectomia , Cistoscopia/métodos , Recidiva Local de Neoplasia/diagnóstico por imagem , Recidiva Local de Neoplasia/patologia , Revisões Sistemáticas como Assunto , Bexiga Urinária/patologia , Neoplasias da Bexiga Urinária/diagnóstico por imagem , Neoplasias da Bexiga Urinária/patologia
2.
Psychiatry Res ; 317: 114860, 2022 11.
Artigo em Inglês | MEDLINE | ID: mdl-36179593

RESUMO

"The Accept Voices© is a useful intervention for the management and acceptance of auditory verbal hallucinations in people with schizophrenia. This study aims at determining if the clinical effects remained at six- and 12-month follow-ups. Results show that participants (N = 22) maintained a decrease in auditory hallucinations, at the six and 12 months follow ups for severity and acceptance of Voices, anxiety and depression. Accept Voices© shows promise as a potential treatment for people with schizophrenia struggling with Voices.


Assuntos
Esquizofrenia , Voz , Humanos , Psicologia do Esquizofrênico , Alucinações/etiologia , Alucinações/terapia , Esquizofrenia/complicações , Esquizofrenia/terapia , Ansiedade/terapia
3.
Vaccine X ; 11: 100187, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-35755140

RESUMO

Background: In December 2020, Sputnik V was incorporated to the National COVID-19 Immunization Plan in Argentina. Studies had shown 98% of antibody response rate. To date, data on immunogenicity and antibody persistence in Argentina are scarce.The objective was to assess humoral immune response after two doses of Sputnik V in Health Care Workers (HCWs) at the Ricardo Gutierrez Children's Hospital (RGCH). Methods: A prospective, cohort study in HCWs immunized with two doses of Sputnik V between February and March 2021. The following variables were assessed: age, gender, risk factors for severe COVID-19 or mortality, immunosuppressive therapy and history of SARS-CoV-2. Blood samples were drawn on the day of the first dose, 28 days and 180 days after the second. Anti-Spike IgG was measured using an ELISA assay. Differences in immune response were evaluated according to study variables. Comparison analyses between groups with or without history of infection were performed, with T-test and ANOVA or Mann-Whitney tests. For each subject, we compared baseline values with 28 days and 180 days after the second vaccine.STATA version 14 and R Sofware were used for data analyses. Results: We included 528 individuals, mean age 41.5 years, 82.9% female, 14.4% (76/528) reported previous SARS-CoV-2 infection.All subjects developed antibodies post-vaccination. At day 28, concentrations were significantly higher in previously infected than naïve subjects (p < 0.001) with no differences according to age, gender and comorbidities.At day 180, 17% (95% CI 13.17-21.53) of naïve subjects were negative. Antibody concentrations decreased significantly in all subjects except in those who reported SARS-CoV-2 infection after vaccination (n = 31). This last group had significantly higher antibody concentrations. Conclusion: This study assessed immune response to a new COVID-19 vaccine in real life in a cohort of subjects. Antibody concentrations varied according to history of SARS-COV-2 infection and decreased over time.

4.
Prog Urol ; 30(16): 1038-1044, 2020 Dec.
Artigo em Francês | MEDLINE | ID: mdl-33012630

RESUMO

PURPOSE: In 2016, the Herault tumor registry collected 1961cancers in urology (21.4 % from all Herault cancers this year). RHESOU was created to complete RTH' data with specific parameters in onco-urology. The aim of this study is to describe RHESOU and to give some examples with our first results. MATERIAL AND METHODS: In November 2018, RHESOU (Registry HErault Specialised in Onco-Urology) was founded with the same registry recommendations. It collects specific oncologic parameters and also complete RTH's data. For each urological cancer, a specific survey with different choices was performed to collect a maximum of data which could be present in patients' file. These surveys were used for urological cancers cases that live in Herault in 2017. RESULTS: In 2017, we collected 970 prostate cancers, 581 bladder cancers, 212 kidney cancers, 51 upper excretory tract cancers, 28 testicle cancers and 9 penil cancers. Our urological data collection gives many possibilities to create many requests for detailed analysis in urological cancers. In this article, we reported data from kidney, bladder and prostate cancers. CONCLUSIONS: RHESOU is a new tool opened to the different urologic corporations (urologists, pathologists, oncologists, radiotherapists, radiologists) that permits an overview in urological cancers in Herault. Finally, one important aim is that this tool will be adapted when new treatments or new important parameters appear in the years ahead. LEVEL OF EVIDENCE: 3.


Assuntos
Oncologia , Sistema de Registros , Neoplasias Urológicas , Feminino , França , Humanos , Neoplasias Renais/diagnóstico , Neoplasias Renais/terapia , Masculino , Neoplasias da Próstata/diagnóstico , Neoplasias da Próstata/terapia , Neoplasias da Bexiga Urinária/diagnóstico , Neoplasias da Bexiga Urinária/terapia , Neoplasias Urológicas/diagnóstico , Neoplasias Urológicas/terapia
5.
Psychiatry Res ; 291: 113159, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32540685

RESUMO

AIM OF THE STUDY: The objective of this study was to evaluate the potential impact of a third wave CBT group intervention for the management of auditory hallucinations in patients with schizophrenia. METHOD: 38 patients with schizophrenia presenting with auditory hallucinations, followed in mental health services, participated in six sessions of a group based on acceptance and engagement therapy (ACT). The study followed a repeated single case experimental design (type A-B-A) based on the principle of a control phase followed by an intervention phase and a follow-up phase of similar duration. The various measurements were administered during the control phase, at pre-/post-group and six weeks after the last group session. RESULTS: The results show a significant decrease in auditory hallucinations, as measured by the PSYRATS scale, during the treatment and follow-up phase, compared to the control phase. In addition, the participants saw significant reductions in depressive and anxious symptomatology (assessed with CDSS and SEAS), and increases in coping and acceptance in regards to voices (assessed using a study scale and VAAS). The level of Malevolence beliefs about voices (measured with BAVQ-R) also decreased significantly. CONCLUSIONS: A brief group intervention based acceptance show promise in the reduction of the intensity of auditory hallucinations, depression and anxiety in patients with schizophrenia, while improving their acceptance.


Assuntos
Terapia Cognitivo-Comportamental/métodos , Gerenciamento Clínico , Alucinações/psicologia , Alucinações/terapia , Esquizofrenia/terapia , Psicologia do Esquizofrênico , Adaptação Psicológica/fisiologia , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Psicoterapia de Grupo/métodos , Inquéritos e Questionários
6.
Encephale ; 46(6): 443-449, 2020 Dec.
Artigo em Francês | MEDLINE | ID: mdl-32192750

RESUMO

OBJECTIVES: Hearing voices is a common experience for people with schizophrenia. Perceived voices are in most cases a source of great distress for patients. This experience also exists in the general population and is considered as "non-clinical". Much research has focused on the psychological and neuropsychological mechanisms behind the emergence of voices. With regard to voice persistence factors, the acceptance of the voice-hearing phenomenon is still relatively unexplored. In addition, there are few standardized tools that specifically assess this dimension of voice experience. The Voices Acceptance and Actions Scale (VAAS) is the only validated tool to address voice acceptance in individuals with schizophrenia. However, to date, there is no French version. The objective of this research was to validate the VAAS in a French speaking population. METHOD: Our sample consisted of individuals with schizophrenia (N=65) and voice hearers from the general population (N=321). For the clinical population, individuals with schizophrenia and auditory hallucinations were assessed using the VAAS scale in its two abbreviated versions (9 and 12 items). In order to validate the measure in French, we administered psychopathology scales (BPRS) and voice belief scales (BAVQ-R) for convergent and divergent validity. For the non-clinical population, we administered the VAAS scale online (via LimeSurvey), accompanied by a brief sociodemographic questionnaire (age, sex, country of origin, existence of medical or psychological follow-up). RESULTS: The psychometric properties of the VAAS scale were satisfactory and similar to the original English-language tool for both versions, with a slight advantage for the one with 9-items. The convergent validity measured with the BAVQ-R scale, and the divergent one measured with the BPRS depression subscale, were found to be satisfactory. In addition, the re-test performed 6 weeks after the first test (N=30) was satisfactory for both scales, with a Pearson correlation index greater than 70 (r=0.70; P<0.001 for the VAAS 9 items) and (r=0.79; P<0.001 for the 12 item version). In individuals with schizophrenia (clinical population), the level of voice acceptance was low and strongly correlated with depression. This point seems to corroborate the current data in the field suggesting that voice hearing in this population is associated with significant distress and has a significant impact on their lives. Conversely, the level of acceptance obtained from the non-clinical population was much higher, reflecting a higher level of acceptance in this population. People from the non-clinical population seemed to accept and experience their voices with less distress than people from the clinical population in this study. CONCLUSION: To date, a paucity of studies have investigated the acceptance of auditory hallucinations. Our results support the psychometric validity of the French version of the VAAS, particularly the 9-item version. Furthermore, our study supports the need to continue studying voice acceptance, as it appears to be strongly linked to depression in people with psychiatric disorders such as schizophrenia. In addition, our study is novel in that it also explored, with a standardized tool, the level of voice acceptance in a non-clinical population and found people to be more accepting of the voices they hear and better at living with them. These data provide new evidence to better understand the links between the level of acceptance of voices, their experiences, and depression. Clinically, it seems essential to conduct more systematic and regular evaluations of the level of voice acceptance in those hearing voices. Finally, in terms of rehabilitation, voice acceptance can become a therapeutic target in order to improve the psychological and behavioral functioning of the person.


Assuntos
Transtornos Mentais , Esquizofrenia , Alucinações/diagnóstico , Humanos , Psicometria , Esquizofrenia/diagnóstico , Inquéritos e Questionários
7.
Nature ; 576(7786): 232-236, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31802002

RESUMO

Remote observations of the solar photospheric light scattered by electrons (the K-corona) and dust (the F-corona or zodiacal light) have been made from the ground during eclipses1 and from space at distances as small as 0.3 astronomical units2-5 to the Sun. Previous observations6-8 of dust scattering have not confirmed the existence of the theoretically predicted dust-free zone near the Sun9-11. The transient nature of the corona has been well characterized for large events, but questions still remain (for example, about the initiation of the corona12 and the production of solar energetic particles13) and for small events even its structure is uncertain14. Here we report imaging of the solar corona15 during the first two perihelion passes (0.16-0.25 astronomical units) of the Parker Solar Probe spacecraft13, each lasting ten days. The view from these distances is qualitatively similar to the historical views from ground and space, but there are some notable differences. At short elongations, we observe a decrease in the intensity of the F-coronal intensity, which is suggestive of the long-sought dust free zone9-11. We also resolve the fine-scale plasma structure of very small eruptions, which are frequently ejected from the Sun. These take two forms: the frequently observed magnetic flux ropes12,16 and the predicted, but not yet observed, magnetic islands17,18 arising from the tearing-mode instability in the current sheet. Our observations of the coronal streamer evolution confirm the large-scale topology of the solar corona, but also reveal that, as recently predicted19, streamers are composed of yet smaller substreamers channelling continual density fluctuations at all visible scales.

8.
Rev Neurol (Paris) ; 175(7-8): 458-463, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31296398

RESUMO

Protein misfolding cyclic amplification assay (PMCA) and real-time quaking-induced conversion (RT-QuIC) are two amplification techniques based on the ability of PrPsc to induce a conformational change in PrP allowing the detection of minute amounts of PrPsc in body fluids or tissues. PMCA and RT-QuIC have different ability to amplify PrPsc from sporadic, variant and genetic forms of Creutzfeldt-Jakob disease (CJD). PMCA readily amplifies PrPsc from variant CJD (vCJD) tissue while RT-QuIC easily amplifies PrPsc from sporadic CJD (sCJD) patient tissues. In terms of diagnosis, this implies the possibility of distinguishing vCJD from sCJD and explains the wider use of RT-QuIC given the respective frequencies of vCJD and sCJD. The sensitivity values of RT-QuIC for the diagnosis of sCJD are comparable or higher than those of the other tests (EEG, MRI, detection of 14-3-3 or tau proteins in cerebrospinal fluid) but with a specificity close to 100%. These new diagnostic methods could also be useful for the diagnosis of other neurodegenerative diseases.


Assuntos
Síndrome de Creutzfeldt-Jakob/diagnóstico , Síndrome de Creutzfeldt-Jakob/microbiologia , Doenças Priônicas/diagnóstico , Doenças Priônicas/microbiologia , Humanos , Técnicas de Diagnóstico Molecular/métodos
9.
Oncogenesis ; 6(7): e366, 2017 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-28759022

RESUMO

miR-151a and its host gene, focal adhesion kinase, FAK, are located in a region of chromosome 8q that is frequently amplified in solid tumors, including lung cancer. Lung cancer is the leading cause of cancer deaths worldwide and metastasis remains the major challenge in battling lung cancer mortality. Here, we demonstrate that miR-151a is overexpressed in non-small cell lung cancer (NSCLC) patient specimens, as compared to healthy lung. In addition, miR-151a overexpression promotes proliferation, epithelial-to-mesenchymal transition (EMT) and induces tumor cell migration and invasion of NSCLC cells. Blocking miR-151a expression using anti-miR-151a approaches significantly reduced NCSLC cell proliferative and motility potential. Furthermore, we determined that miR-151a significantly regulates E-cadherin expression. Finally, functional rescue experiments determined that overexpression of E-cadherin in miR-151a NSCLC cell lines potently repressed miR-151a-induced partial EMT and cell migration of NSCLC cells. In conclusion, our findings suggest that miR-151a functions as an oncomiR in NSCLC by targeting E-cadherin mRNA and inducing proliferation, migration and partial EMT.

10.
Science ; 355(6332): 1392-1395, 2017 03 31.
Artigo em Inglês | MEDLINE | ID: mdl-28325842

RESUMO

The Rosetta spacecraft spent ~2 years orbiting comet 67P/Churyumov-Gerasimenko, most of it at distances that allowed surface characterization and monitoring at submeter scales. From December 2014 to June 2016, numerous localized changes were observed, which we attribute to cometary-specific weathering, erosion, and transient events driven by exposure to sunlight and other processes. While the localized changes suggest compositional or physical heterogeneity, their scale has not resulted in substantial alterations to the comet's landscape. This suggests that most of the major landforms were created early in the comet's current orbital configuration. They may even date from earlier if the comet had a larger volatile inventory, particularly of CO or CO2 ices, or contained amorphous ice, which could have triggered activity at greater distances from the Sun.

11.
Science ; 354(6319): 1566-1570, 2016 12 23.
Artigo em Inglês | MEDLINE | ID: mdl-27856849

RESUMO

The Rosetta spacecraft has investigated comet 67P/Churyumov-Gerasimenko from large heliocentric distances to its perihelion passage and beyond. We trace the seasonal and diurnal evolution of the colors of the 67P nucleus, finding changes driven by sublimation and recondensation of water ice. The whole nucleus became relatively bluer near perihelion, as increasing activity removed the surface dust, implying that water ice is widespread underneath the surface. We identified large (1500 square meters) ice-rich patches appearing and then vanishing in about 10 days, indicating small-scale heterogeneities on the nucleus. Thin frosts sublimating in a few minutes are observed close to receding shadows, and rapid variations in color are seen on extended areas close to the terminator. These cyclic processes are widespread and lead to continuously, slightly varying surface properties.

12.
Ann Oncol ; 27(7): 1235-41, 2016 07.
Artigo em Inglês | MEDLINE | ID: mdl-27029707

RESUMO

BACKGROUND: A minority of early breast cancer (EBC) patients treated with adjuvant or neoadjuvant chemotherapy have sufficient baseline vitamin D (vitD) level. This randomized phase III study assessed the safety and efficacy of a tailored, high-dose, oral vitD supplementation in restoring a normal 25-hydroxy vitD (25OHD) level in this population. PATIENTS AND METHODS: Participants received a 6-month conventional (C) vitD and calcium supplementation or a 6-month high-dose oral vitD regimen tailored on the deficiency (T) and a conventional calcium supplementation. The primary end point was the 6-month percentage of 25OHD serum level normalization. RESULTS: A total of 215 patients including 197 patients with vitD deficiency were recruited, and 195 patients were randomized (T, 100; C, 95). Compliance to the daily oral supplementation was 68.4% and 67% in the C and T arms, respectively. Discontinuous high-dose vitD compliance appeared higher in the T arm (77%). At 6 months, more patients presented with a normalized vitD level in the T arm (30% versus 12.6%; P = 0.003). Supplementation was well tolerated, and no significant difference in the treatment-related toxicity between the two arms was reported. Fifty-two patients without vitD normalization from the C arm switched to the T arm after 6 months. At 12 months, 44% of these patients achieved vitD normalization. CONCLUSION: A tailored high-dose oral vitD supplementation safely allows a higher percentage of the serum 25OHD level normalization compared with a conventional regimen in chemotherapy-treated EBC patients. As compliance to a daily oral supplementation remains poor in this setting, an adaptation of the treatment schedule is warranted. CLINICAL TRIAL NUMBER: NCT01480869.


Assuntos
Neoplasias da Mama/dietoterapia , Suplementos Nutricionais , Deficiência de Vitamina D/dietoterapia , Vitamina D/administração & dosagem , Adulto , Idoso , Neoplasias da Mama/sangue , Neoplasias da Mama/patologia , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/patologia , Feminino , Humanos , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Qualidade de Vida , Vitamina D/análogos & derivados , Vitamina D/sangue , Deficiência de Vitamina D/sangue , Deficiência de Vitamina D/patologia
13.
Prog Urol ; 25(16): 1121-4, 2015 Dec.
Artigo em Francês | MEDLINE | ID: mdl-26475234

RESUMO

INTRODUCTION: With the widespread use of prostate specific antigen (PSA) prescription and despite the automatization of PSA assessment, clinicians should not forget the analytical interference of PSA immunoassays due to the presence of heterophilic autoantibodies in a patient. MATERIAL AND METHODS: This article details some clinical cases, mechanisms involved in the interference and how to overcome this problem. RESULTS: The reported and documented interferences led to useless explorations even erroneous diagnosis. CONCLUSION: Before any unexpected PSA value in relation to the clinical symptomatology, it is strongly recommended to verify the absence of any interference before any invasive procedure or therapy modification.


Assuntos
Antígeno Prostático Específico/sangue , Anticorpos Heterófilos/sangue , Autoanticorpos/sangue , Reações Falso-Positivas , Humanos , Masculino , Neoplasias da Próstata/sangue , Neoplasias da Próstata/diagnóstico
14.
Ann Oncol ; 26(5): 908-914, 2015 May.
Artigo em Inglês | MEDLINE | ID: mdl-25688059

RESUMO

BACKGROUND: This randomized phase II-III trial sought to evaluate the efficacy and safety of adding bevacizumab (Bev) following induction chemotherapy (CT) in extensive small-cell lung cancer (SCLC). PATIENTS AND METHODS: Enrolled SCLC patients received two induction cycles of CT. Responders were randomly assigned 1:1 to receive four additional cycles of CT alone or CT plus Bev (7.5 mg/kg), followed by single-agent Bev until progression or unacceptable toxicity. The primary end point was the percentage of patients for whom disease remained controlled (still in response) at the fourth cycle. RESULTS: In total, 147 patients were enrolled. Partial response was observed in 103 patients, 74 of whom were eligible for Bev and randomly assigned to the CT alone group (n = 37) or the CT plus Bev group (n = 37). Response assessment at the end of the fourth cycle showed that disease control did not differ between the two groups (89.2% versus 91.9% of patients remaining responders in CT alone versus CT plus Bev, respectively; Fisher's exact test: P = 1.00). Progression-free survival (PFS) since randomization did not significantly differ, with a median PFS of 5.5 months [95% confidence interval (CI) 4.9% to 6.0%] versus 5.3 months (95% CI 4.8% to 5.8%) in the CT alone and CT plus Bev groups, respectively [hazard ratio (HR) for CT alone: 1.1; 95% CI 0.7% to 1.7%; unadjusted P = 0.82]. Grade ≥2 hypertension and grade ≥3 thrombotic events were observed in 40% and 11% of patients, respectively, in the CT plus Bev group. Serum vascular endothelial growth factor (VEGF) and soluble VEGF receptor titrations failed to identify predictive biomarkers. CONCLUSION: Administering 7.5 mg/kg Bev after induction did not improve outcome in extensive SCLC patients.


Assuntos
Inibidores da Angiogênese/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Bevacizumab/uso terapêutico , Neoplasias Pulmonares/tratamento farmacológico , Carcinoma de Pequenas Células do Pulmão/tratamento farmacológico , Adulto , Idoso , Inibidores da Angiogênese/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Bevacizumab/efeitos adversos , Cisplatino/uso terapêutico , Ciclofosfamida/uso terapêutico , Progressão da Doença , Intervalo Livre de Doença , Epirubicina/uso terapêutico , Etoposídeo/uso terapêutico , Feminino , França , Humanos , Quimioterapia de Indução , Estimativa de Kaplan-Meier , Neoplasias Pulmonares/mortalidade , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Fatores de Risco , Carcinoma de Pequenas Células do Pulmão/mortalidade , Carcinoma de Pequenas Células do Pulmão/patologia , Fatores de Tempo , Resultado do Tratamento , Adulto Jovem
15.
Oncogene ; 32(31): 3577-86, 2013 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-22926521

RESUMO

One major challenge in cancer research is to understand the complex interplay between the DNA damage response (DDR), genomic integrity, and tumor development. To address these issues, we analyzed 43 bladder tumor genomes from 22 patients using single nucleotide polymorphism (SNP) arrays, and tissue expression of multiple DDR proteins, including Timeless and its interaction partner Tipin. The SNP profiles confirmed and extended known copy number alterations (CNAs) at high resolution, showed clustering of CNAs at nine common fragile sites, and revealed that most metachronous tumors were clonally related. The occurrence of many novel uniparental disomy regions (UPDs) was of potential functional importance in some tumors because UPDs spanned mutated FGFR3 and PIK3CA alleles, and also homozygous deletion of the CDKN2A tumor suppressor locus. The DDR signaling as evaluated by phospho-epitope-specific antibodies against Ser139-phosphorylated H2A histone family member X (γH2AX), ataxia telangiectasia mutated (ATM), and ATM- and Rad3-related (ATR) was commonly activated in tumors with both moderate and high extent of accumulated genomic aberrations, the latter tumors showing a more frequent loss of ATM expression. Strikingly, the tumor genomes exhibiting the most complex alterations were associated with a high Ki67-proliferation index, abundant Timeless but not Tipin expression, aberrant p53 expression, and homozygous CDKN2A deletions. Of clinical relevance, evaluation of a tissue microarray (TMA; n=319) showed that abundant Timeless expression was associated with risk of progression to muscle-invasive disease (P<0.0005; hazard ratio, 2.4; 95% confidence interval, 1.6-3.8) and higher T stage (P<0.05). Univariate analysis confirmed this association (P=0.006) in an independent cohort (n=241) but statistical significance was not reached in a multivariate model. Overall, our results are consistent with DDR activation preceding the accumulation of genomic aberrations. Tumors with extensive genomic rearrangements were associated with inactivation of CDKN2A, excessive proliferation, and robust Timeless expression, the latter also correlating with the risk of disease progression. Moreover, we provide evidence to suggest that UPDs likely contribute to bladder tumorigenesis.


Assuntos
Dano ao DNA/genética , Genômica/métodos , Neoplasias da Bexiga Urinária/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/genética , Proteínas de Transporte/genética , Proteínas de Ciclo Celular/genética , Proliferação de Células , Inibidor de Quinase Dependente de Ciclina p21/metabolismo , Proteínas de Ligação a DNA , Progressão da Doença , Feminino , Predisposição Genética para Doença/genética , Homozigoto , Humanos , Peptídeos e Proteínas de Sinalização Intracelular/genética , Masculino , Pessoa de Meia-Idade , Proteínas Nucleares/genética , Análise de Sequência com Séries de Oligonucleotídeos , Polimorfismo de Nucleotídeo Único , Deleção de Sequência , Transdução de Sinais/genética , Transcriptoma , Proteína Supressora de Tumor p53/metabolismo , Dissomia Uniparental , Neoplasias da Bexiga Urinária/patologia
16.
Oncogene ; 31(22): 2750-60, 2012 May 31.
Artigo em Inglês | MEDLINE | ID: mdl-21963845

RESUMO

Aberrant activation of the Wnt signaling pathway is causally involved in the formation of most colorectal cancers (CRCs). Although detailed knowledge exists regarding Wnt-regulated protein-coding genes, much less is known about the possible involvement of non-coding RNAs. Here we used TaqMan Array MicroRNA Cards, capable of detecting 664 unique human microRNAs (miRNAs), to describe changes of the miRNA transcriptome following disruption of beta-catenin/TCF4 activity in DLD1 CRC cells. Most miRNAs appeared to respond independent of host gene regulation and proximal TCF4 chromatin occupancy as inferred from expression microarray and ChIP-chip data. A module of miRNAs induced by abrogated Wnt signaling in vitro was downregulated in two independent series of human primary CRCs (n=76) relative to normal adjacent mucosa (n=34). Several of these miRNAs (miR-145, miR-126, miR-30e-3p and miR-139-5p) markedly inhibited CRC cell growth in vitro when ectopically expressed. By using an integrative approach of proteomics and expression microarrays, we found numerous mRNAs and proteins to be affected by ectopic miR-30e-3p levels. This included HELZ and PIK3C2A that were directly repressed by several miRNA binding sites as confirmed by luciferase reporter assays in combination with mutational analyses. Finally, small interfering RNA-mediated downregulation of PIK3C2A, but not HELZ, was sufficient on its own to restrict CRC cell growth. Collectively, our study demonstrates that multiple miRNAs are upregulated as a consequence of forced attenuation of Wnt signaling in CRC cells, and some of these miRNAs inhibit cell growth with concomitant suppression of several growth-stimulatory cancer-related genes.


Assuntos
Fatores de Transcrição de Zíper de Leucina e Hélice-Alça-Hélix Básicos/metabolismo , Neoplasias Colorretais/genética , Neoplasias Colorretais/patologia , MicroRNAs/genética , Oncogenes/fisiologia , Fatores de Transcrição/metabolismo , Transcriptoma , beta Catenina/metabolismo , Idoso , Idoso de 80 Anos ou mais , Fatores de Transcrição de Zíper de Leucina e Hélice-Alça-Hélix Básicos/genética , Linhagem Celular Tumoral , Proliferação de Células , Cromatografia Líquida , Colo/metabolismo , Neoplasias Colorretais/metabolismo , Feminino , Perfilação da Expressão Gênica , Genes Dominantes , Humanos , Luciferases/metabolismo , Masculino , Pessoa de Meia-Idade , Análise de Sequência com Séries de Oligonucleotídeos , RNA Mensageiro/genética , RNA Interferente Pequeno , Reto/metabolismo , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz , Fator de Transcrição 4 , Fatores de Transcrição/genética , Células Tumorais Cultivadas , Via de Sinalização Wnt , beta Catenina/genética
17.
Science ; 334(6055): 487-90, 2011 Oct 28.
Artigo em Inglês | MEDLINE | ID: mdl-22034428

RESUMO

Images obtained by the Optical, Spectroscopic, and Infrared Remote Imaging System (OSIRIS) cameras onboard the Rosetta spacecraft reveal that asteroid 21 Lutetia has a complex geology and one of the highest asteroid densities measured so far, 3.4 ± 0.3 grams per cubic centimeter. The north pole region is covered by a thick layer of regolith, which is seen to flow in major landslides associated with albedo variation. Its geologically complex surface, ancient surface age, and high density suggest that Lutetia is most likely a primordial planetesimal. This contrasts with smaller asteroids visited by previous spacecraft, which are probably shattered bodies, fragments of larger parents, or reaccumulated rubble piles.

18.
Science ; 334(6055): 491-2, 2011 Oct 28.
Artigo em Inglês | MEDLINE | ID: mdl-22034429

RESUMO

Asteroid 21 Lutetia was approached by the Rosetta spacecraft on 10 July 2010. The additional Doppler shift of the spacecraft radio signals imposed by 21 Lutetia's gravitational perturbation on the flyby trajectory were used to determine the mass of the asteroid. Calibrating and correcting for all Doppler contributions not associated with Lutetia, a least-squares fit to the residual frequency observations from 4 hours before to 6 hours after closest approach yields a mass of (1.700 ± 0.017) × 10(18) kilograms. Using the volume model of Lutetia determined by the Rosetta Optical, Spectroscopic, and Infrared Remote Imaging System (OSIRIS) camera, the bulk density, an important parameter for clues to its composition and interior, is (3.4 ± 0.3) × 10(3) kilograms per cubic meter.

19.
Encephale ; 37 Suppl 1: S77-82, 2011 May.
Artigo em Francês | MEDLINE | ID: mdl-21600337

RESUMO

BACKGROUND: Borderline personality disorder (BPD) accounts for 10% of outpatient psychiatric practice. The risk of suicide attempts is high and the psychosocial impairment significant. Different theoretical streams have suggested psychotherapeutical approaches for BPD. OBJECTIVE: to examine the efficacy of psychotherapy for BPD patients on affective symptoms, behavioural outcomes, interpersonal and social functioning, as well as BPD criteria. METHODS: We reviewed the medical literature from 1990 to 2008 on Medline by combining the following keywords "borderline personality disorder" and "psychotherapy" (inclusion criteria). We restricted the analysis to "randomised control trial" or "meta analysis". RESULTS: Of the 39 abstracts that came out from the search, we selected 17 (44%) after applying the exclusion criteria. According to our review, different types of psychotherapies have shown some efficacy on reducing affective symptoms and BPD criteria, as well as improving behavioural outcomes and psychosocial functioning. Dialectical behavioural therapy presents the best-documented efficacy, notably on reducing self-mutilating and suicidal behaviours (five randomized controlled trials [RCT]). Mentalization based treatment seems to be efficient on the four types of outcomes, but has been the object of only one RCT. Finally, some evidence suggests that Manual Assisted Cognitive Treatment and Systems Training for Emotional Predictability and Problem Solving are the most cost-effective and easiest to be implemented. CONCLUSION: According to our review, some evidence supports an efficiency of psychotherapies in the management of several features of BPD. It is likely that, depending on the target symptoms, one type of therapy might be more efficient than another. The acceptability of these long-term treatments is however unknown.


Assuntos
Transtorno da Personalidade Borderline/terapia , Psicoterapia/métodos , Afeto , Transtorno da Personalidade Borderline/diagnóstico , Transtorno da Personalidade Borderline/psicologia , Humanos , Relações Interpessoais , Assistência de Longa Duração , Avaliação de Processos e Resultados em Cuidados de Saúde , Ensaios Clínicos Controlados Aleatórios como Assunto , Automutilação/prevenção & controle , Automutilação/psicologia , Ajustamento Social , Comportamento Social , Tentativa de Suicídio/prevenção & controle , Tentativa de Suicídio/psicologia
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