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1.
Recent Results Cancer Res ; 214: 1-70, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31473848

RESUMO

Exploiting the unique specificity of monoclonal antibodies has revolutionized the treatment and diagnosis of haematological and solid organ malignancies; bringing benefit to millions of patients over the past decades. Recent achievements include conjugating antibodies with toxic payloads resulting in superior efficacy and/or reduced toxicity, development of molecular imaging techniques targeting specific antigens for use as predictive and prognostic biomarkers, the development of novel bi- and tri-specific antibodies to enhance therapeutic benefit and abrogate resistance and the success of immunotherapy agents. In this chapter, we review an overview of antibody structure and function relevant to cancer therapy and provide an overview of pivotal clinical trials which have led to regulatory approval of monoclonal antibodies in cancer treatment. We further discuss resistance mechanisms and the unique side effects of each class of antibody and provide an overview of emerging therapeutic agents.


Assuntos
Anticorpos Monoclonais/farmacologia , Imunoterapia , Neoplasias/terapia , Ensaios Clínicos como Assunto , Humanos
2.
Recent Results Cancer Res ; 214: 93-128, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31473850

RESUMO

As a specifically programmable, living immunotherapeutic drug, chimeric antigen receptor (CAR)-modified T cells are providing an alternative treatment option for a broad variety of diseases including so far refractory cancer. By recognizing a tumor-associated antigen, the CAR triggers an anti-tumor response of engineered patient's T cells achieving lasting remissions in the treatment of leukemia and lymphoma. During the last years, significant progress was made in optimizing the CAR design, in manufacturing CAR-engineered T cells, and in the clinical management of patients showing promise to establish adoptive CAR T cell therapy as an effective treatment option in the forefront.


Assuntos
Imunoterapia Adotiva , Neoplasias/terapia , Receptores de Antígenos Quiméricos , Antígenos de Neoplasias/imunologia , Ensaios Clínicos como Assunto , Humanos , Receptores de Antígenos de Linfócitos T , Linfócitos T/imunologia
3.
Recent Results Cancer Res ; 214: 129-151, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31473851

RESUMO

The adoptive cell transfer (ACT) of genetically engineered T cell receptor (TCR) T cells is one of the burgeoning fields of immunotherapy, with promising results in current clinical trials. Presently, clinicaltrials.gov has over 200 active trials involving adoptive cell therapy. The ACT of genetically engineered T cells not only allows the ability to select for TCRs with desired properties such as high-affinity receptors and tumor reactivity but to further enhance those receptors allowing for better targeting and killing of cancer cells in patients. Moreover, the addition of genetic material, including cytokines and cytokine receptors, can increase the survival and persistence of the T cell allowing for complete and sustained remission of cancer targets. The potential for improvement in adoptive cell therapy is limitless, with genetic modifications targeting to improve weaknesses of ACT and to thus enhance receptor affinity and functional avidity of the genetically engineered T cells.


Assuntos
Engenharia Genética , Imunoterapia , Neoplasias/terapia , Receptores de Antígenos de Linfócitos T , Linfócitos T/citologia , Humanos
4.
Recent Results Cancer Res ; 214: 153-167, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31473852

RESUMO

After more than a century of efforts to establish cancer immunotherapy in clinical practice, the advent of checkpoint inhibition (CPI) therapy was a critical breakthrough toward this direction (Hodi et al. in Cell Rep 13(2):412-424, 2010; Wolchok et al. in N Engl J Med 369(2):122-133, 2013; Herbst et al. in Nature 515(7528):563-567, 2014; Tumeh et al. in Nature 515(7528):568-571, 2014). Further, CPIs shifted the focus from long studied shared tumor-associated antigens to mutated ones. As cancer is caused by mutations in somatic cells, the concept to utilize these correlates of 'foreignness' to enable recognition and lysis of the cancer cell by T cell immunity seems an obvious thing to do.


Assuntos
Vacinas Anticâncer , Epitopos/imunologia , Imunoterapia , Neoplasias/terapia , Antígenos de Neoplasias/imunologia , Humanos
5.
Rev. Pesqui. (Univ. Fed. Estado Rio J., Online) ; 11(5): 1376-1382, out.-dez. 2019. il
Artigo em Inglês, Português | LILACS, BDENF - Enfermagem | ID: biblio-1021840

RESUMO

Objective: The study's goal has been to identify in the literature the use of auriculotherapy with needles as an intervention to improve cancer patients' life quality. Methods: It is an Integrative Literature Review of articles published in Portuguese, English, Spanish and/or German, available in full at the databases VHL, CAPES, CINHAL, PubMed, Web of Science and Scopus. The study was carried out in January 2017. The descriptors employed were cancer, neoplasms, auriculotherapy, ear acupuncture, and auricular acupuncture, and six studies were then selected. Results: The use of auricular therapy with needles as interventions in the clinical symptoms due to cancer and its treatment, as well as in the improvement of the domains affected in people's life quality have indicated satisfactory evidence. Conclusion: The evidences have identified an improvement in the quality of life of oncology patients that underwent auriculotherapy with needles, therefore, this intervention is a safe, effective and economical complementary therapy, which is very well accepted by the patients


Objetivo: Identificar na literatura o uso da auriculoterapia com agulhas como intervenção para melhoria da qualidade de vida de pacientes com câncer. Método: Revisão integrativa de artigos publicados em português, inglês, espanhol e/ou alemão, disponíveis na íntegra nas bases de dados BVS, CAPES, CINHAL, PUBMED, WEB of SCIENCE e SCOPUS. A pesquisa ocorreu no período de janeiro de 2017. Foram utilizados os descritores câncer, neoplasia, auriculoterapia, acupuntura orelha e acupuntura auricular, sendo selecionados seis estudos. Resultados: O uso da auriculoterapia com agulhas como intervenções nos sintomas clínicos decorrentes do câncer e de seu tratamento bem como na melhoria dos domínios afetados na qualidade de vida apontou evidências satisfatórias. Conclusão: As evidências identificaram melhora na qualidade de vida de pacientes oncológicos que foram submetidos a auriculoterapia com agulhas e que esta intervenção é uma terapia complementar segura, eficaz e econômica, muito bem aceita pelos pacientes


Objetivo: Identificar la producción disponible relacionada al uso de la acupuntura auricular como intervención para la mejora de la calidad de vida de pacientes con cáncer. Método: Revisión integrativa de literatura con búsqueda en bases electrónicas y bibliotecas virtuales BVS, CAPES, CINHAL, PUBMED, WEB of SCIENCE y SCOPUS En el período de enero de 2017 con los descriptores cáncer, neoplasia, auriculoterapia, acupuntura o acupuntura auricular y acupuntura auricular, la acupuntura auricular y la acupuntura auricular. La revisión integrativa propuesta tuvo lugar en seis etapas distintas y complementarias. Resultados: Se identificaron seis artículos con evidencias satisfactorias de las intervenciones en los síntomas clínicos inherentes al cáncer y su tratamiento que demostraron impactos positivos de la auriculoterapia como intervención. Conclusión: Los estudios relacionados con el tema son escasos, apuntan una realidad científica poco explorada. Un número mayor de estudios clínicos debe ocurrir para fortalecer las evidencias de las intervenciones terapéuticas efectivas, subsidiar la práctica y asegurar asistencia cualificada


Assuntos
Humanos , Acupuntura Auricular , Auriculoterapia/tendências , Neoplasias/terapia , Assistência ao Paciente
6.
Adv Exp Med Biol ; 1164: 179-196, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31576549

RESUMO

DNA methylation is a chemically reversible epigenetic modification that regulates the chromatin structure and gene expression, and thereby takes part in various cellular processes like embryogenesis, genomic imprinting, X-chromosome inactivation, and genome stability. Alterations in the normal methylation levels of DNA may contribute to the development of pathological conditions like cancer. Even though both hypo- and hypermethylation-mediated abnormalities are prevalent in the cancer genome, the field of cancer epigenetics has been more focused on targeting hypermethylation. As a result, DNA hypomethylation-mediated abnormalities remained relatively less explored, and currently, there are no approved drugs that can be clinically used to target hypomethylation. Understanding the precise role of DNA hypomethylation is not only crucial from a mechanistic point of view but also for the development of pharmacological agents that can reverse the hypomethylated state of the DNA. This chapter focuses on the causes and impact of DNA hypomethylation in the development of cancer and describes the possible ways to pharmacologically target it, especially by using a naturally occurring physiologic agent S-adenosylmethionine (SAM).


Assuntos
Metilação de DNA , Epigênese Genética , Neoplasias , Epigenômica , Humanos , Neoplasias/genética , Neoplasias/terapia
7.
Medicine (Baltimore) ; 98(38): e17228, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31567984

RESUMO

OBJECTIVE: To determine whether psychological intervention (PI) changes the levels of immune indicators in cancer patients. METHODS: We conducted a systematic search published up to July 2018, followed by a manual search. Randomized controlled trials were included. Two reviewers independently screened and extracted data, which were analyzed using Review manager 5.3. RESULTS: Twenty-nine studies were included including four kinds of PI. Only stress management didn't result in immune changes; only cognitive behavior therapy affect NK cell activity. PI did not change immune indicators on cancer patients who completed therapy. Compared to patients not receiving PI, those received PI had significantly higher NK cell count and activity in whole blood; and serum levels of IL-2, IL-4, IFN-γ, lgA, and lgG. However, the differences in the serum levels of IL-6, IL-10, TNF-α, and IgM were not significant (P > .05), and the changes recorded for the CD3, CD4, and CD8 cell count, and CD4/CD8 ratios were inconsistent. CONCLUSIONS: Although there are considerable evidences of PI's immune effect, but its magnitude was moderate. Therefore, it may be premature to conclude whether PI affects immunity of cancer patients. Further research is warranted, with special focus on the PI types and treatment methods.


Assuntos
Neoplasias/psicologia , Psicoterapia , Humanos , Imunidade , Neoplasias/imunologia , Neoplasias/terapia , Psicoterapia/métodos
8.
Soins Gerontol ; 24(139): 19-21, 2019.
Artigo em Francês | MEDLINE | ID: mdl-31540716

RESUMO

Combining quality and quantity of life is one of the challenges of geriatric oncology This requires early diagnosis and a full medical, psychological and social assessment of the patient. The aim of this assessment is to take a global approach to the patient's care management, to take into consideration his or her own opinion and to define a suitable treatment. Once the treatment has been established, the setting up of follow-up care for any comorbidities and symptoms, as well as the putting in place of help where needed, can help to improve quality of life.


Assuntos
Neoplasias/terapia , Qualidade de Vida , Idoso , Humanos , Oncologia
9.
Cancer Radiother ; 23(6-7): 496-499, 2019 Oct.
Artigo em Francês | MEDLINE | ID: mdl-31471251

RESUMO

Stereotactic radiotherapy of oligometastases, mono- or hypofractionated, represents a fundamental change in the practice of the specialty as it was developed for a century. Despite the great heterogeneity of sites, techniques, and doses, most studies found a high local control rate, around 70 to 90% at 2 years, and reduced toxicity, around 5% of grade 3 at 2 years. Four main phase II and III trials are underway in France. Future research concerns the association of stereotactic radiotherapy with immunotherapy or different conventional chemotherapy protocols, the identification of the best clinical presentations, and optimization of fractionation and biological dose for poor prognosis localizations.


Assuntos
Ensaios Clínicos Fase II como Assunto , Ensaios Clínicos Fase III como Assunto , Neoplasias/radioterapia , Radiocirurgia/métodos , Ensaios Clínicos Controlados Aleatórios como Assunto , Anticorpos Monoclonais/uso terapêutico , Antineoplásicos Imunológicos/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Ósseas/radioterapia , Neoplasias Ósseas/secundário , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/radioterapia , Terapia Combinada/métodos , Previsões , França , Humanos , Imunoterapia , Neoplasias Renais/tratamento farmacológico , Neoplasias Renais/radioterapia , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/radioterapia , Masculino , Metástase Neoplásica , Neoplasias/patologia , Neoplasias/terapia , Neoplasias da Próstata/tratamento farmacológico , Neoplasias da Próstata/radioterapia , Carcinoma de Células Escamosas de Cabeça e Pescoço/tratamento farmacológico , Carcinoma de Células Escamosas de Cabeça e Pescoço/radioterapia
10.
Rev Med Suisse ; 15(660): 1512-1515, 2019 Aug 28.
Artigo em Francês | MEDLINE | ID: mdl-31496176

RESUMO

The emergence of immunotherapy has generated great enthusiasm in oncology improving the prognosis of pathologies such as melanoma, lung cancer, kidney cancer, bladder and head and neck cancers. This enthusiasm concerns also older patients in view of the good tolerance of immunotherapy in young people. However, advanced age is linked to changes in the immune system, called immunosenescence, which could have a negative impact on the efficacy and toxicity of immunotherapy treatment. Knowledge in terms of efficacy and tolerance is limited for geriatric patients, few being included in clinical studies. This article summarizes the experience of immunotherapy in large clinical trials. It appears that the immune checkpoint inhibitors are effective and well tolerated in the elderly.


Assuntos
Imunoterapia , Neoplasias , Fatores Etários , Humanos , Tolerância Imunológica , Imunossenescência , Oncologia/tendências , Neoplasias/terapia
11.
Cancer Radiother ; 23(6-7): 662-665, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31473087

RESUMO

Chemoradiotherapy is now considered the standard of care for many locally advanced diseases. Cytotoxic drugs have been largely evaluated in this setting, with cisplatin and 5FU the most often used drugs. A large amount of pre-clinical studies has demonstrated the synergy between both modalities. Concomitant administration seems the more beneficial in many diseases. Emergence of new approaches, combining targeted therapies and radiotherapy (RT) is now a reality. The main example is the association of cetuximab and RT in head and neck carcinomas, even if, 14 years after the initial publication, the best way to use it is still unknown. New compounds as inhibitors of DNA-repair or immune checkpoints are under investigation and showed early promising results.


Assuntos
Antineoplásicos/administração & dosagem , Quimiorradioterapia/tendências , Neoplasias/terapia , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Cetuximab/administração & dosagem , Quimiorradioterapia/métodos , Cisplatino/administração & dosagem , Reparo do DNA/efeitos dos fármacos , Docetaxel/administração & dosagem , Esquema de Medicação , Fluoruracila/administração & dosagem , Humanos , Terapia de Alvo Molecular/métodos , Órgãos em Risco/efeitos da radiação , Lesões por Radiação/prevenção & controle , Fatores de Tempo
13.
Ther Umsch ; 76(4): 167-172, 2019 Sep.
Artigo em Alemão | MEDLINE | ID: mdl-31498036

RESUMO

Nuclear medicine diagnostics, therapy and theranostics in the context of modern oncology Abstract. Nuclear medicine deals with imaging, therapy and theranostics using radioactive elements bound to targeted carrier molecules, so-called radiotracers. Modern oncology in particular benefits from the increasing diagnostic possibilities, for example in the context of increasingly precise tumour spread diagnostics or the early measurement of tumour response under targeted therapies. Modern nuclear medicine also offers new and innovative methods for the treatment of special types of tumours. For example, new therapies are available to treat metastatic prostate cancer, while other methods, such as breast and lung cancer or pancreatic cancer, are currently being tested in clinical trials. Nuclear medicine is complemented by theranostics, which combines therapeutic and diagnostic methods. Particularly in modern, personalized oncology with all its targeted therapies, these methods benefit from predicting therapy and high response rates.


Assuntos
Neoplasias/diagnóstico , Neoplasias/terapia , Medicina Nuclear , Nanomedicina Teranóstica , Humanos , Oncologia , Terapia de Alvo Molecular
14.
Ther Umsch ; 76(4): 187-194, 2019 Sep.
Artigo em Alemão | MEDLINE | ID: mdl-31498037

RESUMO

Immunotherapies - Overview, mode of action and clinical implications Abstract. The introduction of immunotherapies has led to major advances in the treatment of cancer patients. The mainstays of immunotherapies in clinical routine are immune checkpoint inhibitors. Immune checkpoints like CTLA-4 or the PD-1 / PD-L1 axis are important contributors to the immune homeostasis by preventing overshooting immune responses against pathogens and thus preventing collateral damage to normal tissue, or by preventing autoimmunity. However, immune checkpoints can impede the development of an efficient anti-tumor immune response. Thus, therapeutic monoclonal antibodies against CTLA-4 and PD-1 or PD-L1 displayed remarkable clinical activity such as complete sustained clinical remission even in patients bearing multiple metastases. Malignant melanoma, non-small cell lung cancer or Hodgkin's lymphoma are examples of cancer entities with especially well clinical responses to immune checkpoint inhibitors. This fast-developing field is rapidly expanding the indications for immune checkpoint inhibitors and combinations with other therapeutic strategies like vessel-modulating agents or classical chemotherapy are in preclinical and clinical testing. In this article, the mechanistic principles of immune checkpoint inhibition and their clinical applications are illustrated.


Assuntos
Imunoterapia , Neoplasias/terapia , Anticorpos Monoclonais/uso terapêutico , Antineoplásicos/uso terapêutico , Antígeno CTLA-4/antagonistas & inibidores , Humanos , Imunoterapia/métodos
15.
Ther Umsch ; 76(4): 179-185, 2019 Sep.
Artigo em Alemão | MEDLINE | ID: mdl-31498038

RESUMO

Molecularly-targeted anticancer treatments - a short appraisal Abstract. Molecularly-targeted or personalized systemic treatment has substantially transformed modern oncology, and has improved the prognosis of many tumor entities, in particular advanced solid and hematological malignancies. The bulk of molecularly-targeted anticancer drugs comprise small orally administered molecules, most prominently the tyrosine kinase inhibitors (TKI). The respective tumor entities treated by those drugs typically harbour specific genetic aberrations that we often call 'driver mutations', referring to their transforming and tumorigenic properties. Molecularly-targeted anticancer drugs fit to these genetic aberrations as they are able to specifically inhibit growth-stimulating signals. The success story of modern TKI's started 1999 with the use of the anti-BCR / ABL TKI imatinib in chronic myelogenous leucemia (CML) that enables those patients to achieve a virtually normal life expectancy. Since then, many molecularly-targeted anticancer drugs and TKI's have been approved for a wide range of malignancies. The next level of personalized oncological treatment will have to deal with much less frequent genetic aberrations that are inherently more difficult to spot in the tumor and to study. Newer techniques including next-generation sequencing (NGS) will help cancer specialists to screen their patients for genetic aberrations and get the most benefit from personalized oncology.


Assuntos
Antineoplásicos , Terapia de Alvo Molecular , Neoplasias/diagnóstico , Neoplasias/terapia , Medicina Nuclear , Resistencia a Medicamentos Antineoplásicos , Humanos , Oncologia
16.
Ther Umsch ; 76(4): 195-198, 2019 Sep.
Artigo em Alemão | MEDLINE | ID: mdl-31498041

RESUMO

Immunotherapy - immune-related adverse events and their management Abstract. Checkpoint-Inhibition has become an important part of modern oncological treatment strategies for many patients with cancer. The development of this new class of anti-cancer drugs has begun for ten years and showed meanwhile a specific new side effect profile. Since the mode of action of checkpoint inhibitors is immune modulation the side effects are particularly different to so far established anti-cancer drugs. Because of the immunological nature of side effects, the spectrum is wide, and the symptoms are amble. Additionally, the side effects can appear at very different time points after the administration of the checkpoint inhibitor. Therefore, the recognition and the management are a new challenge for the care teams. Only if the whole care team is able to understand, diagnose and efficiently manage the side effects the therapeutic potential of this new class of anti-cancer drugs can be made useful for the patients. The article aims to provide information for the care teams to recognize and manage side effects of checkpoint-inhibitors.


Assuntos
Imunoterapia/efeitos adversos , Imunoterapia/métodos , Neoplasias/terapia , Humanos , Fatores Imunológicos , Oncologia , Síndromes Neurotóxicas/etiologia
18.
Adv Exp Med Biol ; 1148: 173-199, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31482500

RESUMO

Cancer treatment has greatly improved over the last 50 years, but it remains challenging in several cases. Useful therapeutic targets are normally unique peculiarities of cancer cells that distinguish them from normal cells and that can be tackled with appropriate drugs. It is now known that cell metabolism is rewired during tumorigenesis and metastasis as a consequence of oncogene activation and oncosuppressors inactivation, leading to a new cellular homeostasis typically directed towards anabolism. Because of these modifications, cells can become strongly or absolutely dependent on specific substrates, like sugars, lipids or amino acids. Cancer addictions are a relevant target for therapy, as removal of an essential substrate can lead to their selective cell-cycle arrest or even to cell death, leaving normal cells untouched. Enzymes can act as powerful agents in this respect, as demonstrated by asparaginase, which has been included in the treatment of Acute Lymphoblastic Leukemia for half a century. In this review, a short outline of cancer addictions will be provided, focusing on the main cancer amino acid dependencies described so far. Therapeutic enzymes which have been already experimented at the clinical level will be discussed, along with novel potential candidates that we propose as new promising molecules. The intrinsic limitations of their present molecular forms, along with molecular engineering solutions to explore, will also be presented.


Assuntos
Aminoácidos/química , Enzimas/farmacologia , Neoplasias/terapia , Asparaginase , Terapia Enzimática , Humanos , Neoplasias/metabolismo , Leucemia-Linfoma Linfoblástico de Células Precursoras
19.
Gan To Kagaku Ryoho ; 46(8): 1230-1234, 2019 Aug.
Artigo em Japonês | MEDLINE | ID: mdl-31501362

RESUMO

Patient participation is defined as incorporation of opinions by patients and citizens when clinical trials are planning. It has been early established in the USA and the UK. The Japan Clinical Oncology Group(JCOG)has recently launched a subcommittee of patient participation and has tried to input opinions of patients and citizens in clinical trials. We, Hepatobiliary and Pancreatic Oncology Group in JCOG, has held 3 meetings of patient participation for 3 years. We introduced our policy and clinical trials and discussed off-label drugs or treatments. In the third meeting in 2019, we have discussed precision medicine using genome analysis and clinical trials which are currently planning in our group. There are some significances and expectations to patient participation from the points of views of researchers. It is meaning to pick up clinicalunmet medicalneeds from patient participation and input requests and opinions of patients to a protocol. Opinions of patients and citizens may be useful to make informed consent form easy to read and understand for patients and their family. In order to accelerate recruitment of patients in clinical trials, it is important that patients and citizens understand exactly clinical trials through patient participation. Patient participation has just begun in Japan. It is expected to establish Japanese patient participation in the near future. It is important for not only researchers but also patients to obtain some benefits from patient participation.


Assuntos
Neoplasias/terapia , Humanos , Consentimento Livre e Esclarecido , Japão , Oncologia , Médicos , Medicina de Precisão
20.
Gan To Kagaku Ryoho ; 46(8): 1275-1279, 2019 Aug.
Artigo em Japonês | MEDLINE | ID: mdl-31501369

RESUMO

BACKGROUND: The gap between patients' and physicians' expectations from treatment has been a difficult problem in oncology because it affects decision-making. This study identified patients' expectations from their treatment and concerns when palliative chemotherapy was initiated. METHODS: Patients completed a questionnaire, which included open-ended questions about their expectations from the treatment and their biggest concerns at that moment after a clear explanation that the nature of their metastatic or recurrent cancer treatment was palliative and not curative. One hundred and sixty-five consecutive Japanese patients were included in this study. RESULTS: Twenty-nine percent of the patients described their expectation as "symptomatic improvement,"28% as"objective treatment effect,"and 19%as"cure."The most common concern was the toxicity(41%). No significant change was revealed in later-line treatment. CONCLUSION: The patients' expectation from palliative chemotherapy and concerns should be considered more precisely in each phase. Dedicated palliative care and explanation of toxicity controlon the initiation of treatments are essential.


Assuntos
Motivação , Neoplasias , Tomada de Decisões , Humanos , Neoplasias/terapia , Cuidados Paliativos , Inquéritos e Questionários
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