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3.
Bull Cancer ; 107(1): 6-9, 2020 Jan.
Artigo em Francês | MEDLINE | ID: mdl-31954504

RESUMO

In this brief note, we review the state of knowledge about biomarkers that influence the response to current immunotherapies and the impact of recent technological developments (single-cell analysis, multi-dimensional imaging) on the analysis of these biomarkers. Also, new developments and strategies around CAR-T cells and bispecific antibodies in immuno-oncology are presented.


Assuntos
Imunoterapia/tendências , Oncologia/tendências , Neoplasias/terapia , Pesquisa/tendências , Anticorpos Biespecíficos/uso terapêutico , Antineoplásicos Imunológicos/uso terapêutico , Biomarcadores Tumorais , Gerenciamento Clínico , Humanos , Imunoterapia/métodos , Imunoterapia Adotiva , Terapia de Alvo Molecular , Neoplasias/química , Terapias em Estudo
4.
Bull Cancer ; 107(1): 129-135, 2020 Jan.
Artigo em Francês | MEDLINE | ID: mdl-31882268

RESUMO

Chordomas are rare malignant tumours, which typically occur in the axial skeleton and skull base. They arise from embryonic remnants of the notochord. They constitute less than 5 % of primary bone tumours. They are characterised by their locally aggressive potential with high frequency of recurrences and a median overall survival of 6 years. The initial therapeutic strategy must be discussed in an expert centre and may involve surgery, preoperative radiotherapy, exclusive radiotherapy or therapeutic abstention. Despite this, more than 50 % of patients will be facing recurrences with few therapeutic options available at this advanced stage. This review aims to outline current treatment options available in chordomas, as well as discussing potentiality of new therapeutic approaches through their molecular characterization and the comprehension of their immunological environment.


Assuntos
Neoplasias Ósseas/terapia , Cordoma/terapia , Pesquisa Médica Translacional , Biomarcadores Tumorais , Neoplasias Ósseas/embriologia , Neoplasias Ósseas/genética , Neoplasias Ósseas/imunologia , Cordoma/embriologia , Cordoma/genética , Cordoma/imunologia , Terapia Combinada , Humanos , Terapia de Alvo Molecular , Proteínas de Neoplasias/genética , Notocorda/patologia , Recidiva , Terapia de Salvação , Terapias em Estudo
5.
Ann Hematol ; 98(11): 2467-2483, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31667544

RESUMO

A significant proportion of adult patients with acute myeloid leukemia (AML) fail to achieve complete remission or will relapse later on after achieving it. Prognosis for relapsed or refractory (R/R) AML patients remains discouraging, with the main curative option still relying on hematopoietic stem cell transplant (HSCT) for those who are eligible. Beyond morphological bone marrow and peripheral blood assessment, evaluation of patient performance status and comorbidities, as well as genetic/molecular characterization, is crucial to make an accurate diagnosis and prognosis, which will be useful to select the most appropriate treatment. Emerging strategies are mainly focusing on the development of immune- and molecular-based approaches. Novel targeted therapies are generally well tolerated, potentially allowing them to be administered alone or in combination with classical chemotherapy agents. Enrolment in clinical trials should be considered first option for R/R AML patients, either as a bridge to HSCT or to benefit from novel therapies that eventually may prolong survival and improve quality of life. An Iberian expert panel has reviewed the recent advances in the management of R/R AML with the aim to develop updated evidence and expert opinion-based recommendations.


Assuntos
Antineoplásicos/uso terapêutico , Leucemia Mieloide Aguda/terapia , Terapia de Salvação , Terapias em Estudo , Adulto , Idoso , Aloenxertos , Antineoplásicos/classificação , Terapia Combinada , Quimioterapia de Consolidação , Gerenciamento Clínico , Epigênese Genética/efeitos dos fármacos , Transplante de Células-Tronco Hematopoéticas , Humanos , Leucemia Mieloide Aguda/diagnóstico , Leucemia Mieloide Aguda/tratamento farmacológico , Leucemia Mieloide Aguda/genética , Pessoa de Meia-Idade , Mitocôndrias/efeitos dos fármacos , Terapia de Alvo Molecular , Prognóstico , Recidiva , Indução de Remissão , Fatores de Risco , Índice de Gravidade de Doença
8.
World J Gastroenterol ; 25(32): 4580-4597, 2019 Aug 28.
Artigo em Inglês | MEDLINE | ID: mdl-31528088

RESUMO

Chronic delta hepatitis is the most severe form of viral hepatitis affecting nearly 65 million people worldwide. Individuals with this devastating illness are at higher risk for developing cirrhosis and hepatocellular carcinoma. Delta virus is a defective RNA virus that requires hepatitis B surface antigen for propagation in humans. Infection can occur in the form of a co-infection with hepatitis B, which can be self-limiting, vs superinfection in a patient with established hepatitis B infection, which often leads to chronicity in majority of cases. Current noninvasive tools to assess for advanced liver disease have limited utility in delta hepatitis. Guidelines recommend treatment with pegylated interferon, but this is limited to patients with compensated disease and is efficacious in about 30% of those treated. Due to limited treatment options, novel agents are being investigated and include entry, assembly and export inhibitors of viral particles in addition to stimulators of the host immune response. Future clinical trials should take into consideration the interaction of hepatitis B and hepatitis D as suppression of one virus can lead to the activation of the other. Also, surrogate markers of treatment efficacy have been proposed.


Assuntos
Antivirais/uso terapêutico , Coinfecção/tratamento farmacológico , Hepatite B Crônica/tratamento farmacológico , Hepatite D Crônica/tratamento farmacológico , Superinfecção/tratamento farmacológico , Terapias em Estudo/métodos , Antivirais/farmacologia , Coinfecção/epidemiologia , Coinfecção/virologia , Quimioterapia Combinada/métodos , Carga Global da Doença , Antígenos de Superfície da Hepatite B/imunologia , Antígenos de Superfície da Hepatite B/metabolismo , Vírus da Hepatite B/imunologia , Vírus da Hepatite B/patogenicidade , Hepatite B Crônica/epidemiologia , Hepatite B Crônica/virologia , Hepatite D Crônica/epidemiologia , Hepatite D Crônica/virologia , Vírus Delta da Hepatite/imunologia , Vírus Delta da Hepatite/patogenicidade , Humanos , Interferon-alfa/farmacologia , Interferon-alfa/uso terapêutico , Lipopeptídeos/farmacologia , Lipopeptídeos/uso terapêutico , Transportadores de Ânions Orgânicos Dependentes de Sódio/antagonistas & inibidores , Transportadores de Ânions Orgânicos Dependentes de Sódio/metabolismo , Piperidinas/farmacologia , Piperidinas/uso terapêutico , Piridinas/farmacologia , Piridinas/uso terapêutico , Ensaios Clínicos Controlados Aleatórios como Assunto , Literatura de Revisão como Assunto , Superinfecção/epidemiologia , Superinfecção/virologia , Simportadores/antagonistas & inibidores , Simportadores/metabolismo , Resultado do Tratamento , Montagem de Vírus/efeitos dos fármacos , Internalização do Vírus/efeitos dos fármacos
9.
Nat Rev Clin Oncol ; 16(12): 773-778, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31477881

RESUMO

For many years, oncology phase I trials have been referred to as 'toxicity trials' and have been believed to have low clinical utility other than that of establishing the adverse event profile of novel therapeutic agents. The traditional distinction of clinical trials into three phases has been challenged in the past few years by the introduction of targeted therapies and immunotherapies into the routine management of patients with cancer. This transformation has especially affected early phase trials, leading to the current situation in which response rates are increasingly reported from phase I trials. In this Perspectives, we highlight key elements of phase I trials and discuss how each one of them contributes to a new paradigm whereby preliminary measurements of the clinical benefit from a novel treatment can be obtained in current phase I trials, which can therefore be considered to have a therapeutic intent.


Assuntos
Ensaios Clínicos Fase I como Assunto , Neoplasias/terapia , Comportamento de Escolha , Ensaios Clínicos Fase I como Assunto/métodos , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/prevenção & controle , Drogas em Investigação/efeitos adversos , Humanos , Imunoterapia/efeitos adversos , Imunoterapia/métodos , Imunoterapia/tendências , Oncologia/métodos , Oncologia/tendências , Terapia de Alvo Molecular/efeitos adversos , Terapia de Alvo Molecular/métodos , Terapia de Alvo Molecular/tendências , Terapias em Estudo/métodos , Terapias em Estudo/tendências
11.
J Bioeth Inq ; 16(3): 463-466, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31444643

RESUMO

This comment responds to a defence of the right to try, a law adopted by the United States and many state governments that seeks to expand access to experimental drugs. In defending the right to try, Meyerson argues that it is part of a broader rights-based approach for patient access to innovation. But a drug that is still part of the experimental process may not be an innovation-indeed, it may be a failure and even harmful or dangerous. Further, this approach does not weigh other rights that may be at stake such as the property rights of the drug maker or the rights of future patients seeking access to cures. Lastly, research has found that many patients often fail to receive recommended treatments and preventive care from their providers, let alone experimental or innovative therapies. These policy problems suggest that there is a need for patients to have a greater involvement and role in their care and in how research funding is made, but the right to try fails to address these problems.


Assuntos
Pesquisa Biomédica , Imperícia , Humanos , Terapias em Estudo , Estados Unidos
12.
Presse Med ; 48(7-8 Pt 1): 807-815, 2019.
Artigo em Francês | MEDLINE | ID: mdl-31447332

RESUMO

Chronic lymphocytic leukemia is the most frequent adult leukemia. Eighty per cent of the patients are asymptomatic at diagnosis and 30% of the patients will be never treated. The diagnosis is based on the blood smear examination and immunophenotyping by flow cytometry of blood lymphocytes. The first line option is immunochemotherapy in 90% of the patients without genetic abnormalities associated with chemo resistance. The use of new compounds targeting different pathways is more frequent especially in relapsing patients and could be an alternative to the chemotherapy in the future. Asymptomatic patients with a stable disease assessed by the specialist can be followed by the general practitioner with a blood count and clinical examination every six months or once a year.


Assuntos
Leucemia Linfocítica Crônica de Células B , Anticorpos Monoclonais/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Diagnóstico Diferencial , Humanos , Imunofenotipagem/métodos , Imunoterapia , Leucemia Linfocítica Crônica de Células B/classificação , Leucemia Linfocítica Crônica de Células B/diagnóstico , Leucemia Linfocítica Crônica de Células B/patologia , Leucemia Linfocítica Crônica de Células B/terapia , Terapia de Alvo Molecular/métodos , Terapia de Alvo Molecular/tendências , Prognóstico , Inibidores de Proteínas Quinases/uso terapêutico , Terapias em Estudo/métodos , Terapias em Estudo/tendências
13.
Presse Med ; 48(7-8 Pt 1): 850-858, 2019.
Artigo em Francês | MEDLINE | ID: mdl-31447334

RESUMO

Follicular lymphoma, the second most common lymphoma, is characterized by its slow growth and is often considered incurable in advanced stages. Progresses in biology have contributed to better understand the complex and successive mechanisms of development of this pathology, whose diagnosis is based on a lymph node biopsy. However, the prognosis of the patients is heterogeneous and several indexes have been proposed to identify groups of patients with a similar life expectancy, in order to guide the therapeutic choices. The treatment has been modified in the last 20 years by the emergence of anti-CD20 monoclonal antibodies which constitute, alone or in combination, of the cornerstone of therapeutic management. After staging using, in particular, 18-fluorodeoxyglucose positron emission tomography, the therapeutic strategy will be adapted for each patient, ranging from simple watchful waiting to a combination of chemotherapy and anti-CD20 antibodies. Relapses (which often require a new lymph node biopsy to eliminate a possible histological transformation into an aggressive lymphoma with poorer prognosis) remain common but are still accessible to effective therapeutic interventions. Thanks to these advances, the median life expectancy of patients with follicular lymphoma now exceeds 15 years.


Assuntos
Linfoma Folicular , Biópsia , Diagnóstico Diferencial , Humanos , Imunofenotipagem/métodos , Imunoterapia/métodos , Imunoterapia/tendências , Expectativa de Vida , Linfoma Folicular/diagnóstico , Linfoma Folicular/epidemiologia , Linfoma Folicular/patologia , Linfoma Folicular/terapia , Técnicas de Diagnóstico Molecular , Recidiva Local de Neoplasia/epidemiologia , Recidiva Local de Neoplasia/terapia , Medicina de Precisão/métodos , Medicina de Precisão/tendências , Prognóstico , Taxa de Sobrevida , Terapias em Estudo/métodos , Terapias em Estudo/tendências
14.
Presse Med ; 48(7-8 Pt 1): 825-831, 2019.
Artigo em Francês | MEDLINE | ID: mdl-31447337

RESUMO

Diagnosis criteria have been revised in 2014 and allow the treatment of some asymptomatic patients. Since 2015, a new prognostic score includes tumor plasma cells chromosomal abnormalities. It helps in the distinction between "standard risk" and "high risk" myelomas. Scanner, MRI and Pet Scan are the radiological reference exams to evaluate bone involvement. Alkylating agents, immunomodulators, proteasome inhibitors, and monoclonal antibodies became the most important antitumoral treatments. Risk notion will become more and more important for therapeutic choices. These choices will depend on residual disease evaluation. The next decade will be the immunotherapies development decade.


Assuntos
Detecção Precoce de Câncer/tendências , Oncologia/tendências , Mieloma Múltiplo/diagnóstico , Mieloma Múltiplo/terapia , Terapias em Estudo/tendências , Anticorpos Monoclonais/uso terapêutico , Terapia Combinada/tendências , Detecção Precoce de Câncer/métodos , Detecção Precoce de Câncer/normas , Humanos , Fatores Imunológicos/uso terapêutico , Imunoterapia/métodos , Imunoterapia/tendências , Oncologia/métodos , Oncologia/normas , Mieloma Múltiplo/patologia , Guias de Prática Clínica como Assunto , Prognóstico , Terapias em Estudo/métodos
15.
Int J Mol Sci ; 20(15)2019 Aug 03.
Artigo em Inglês | MEDLINE | ID: mdl-31382625

RESUMO

Several expedited regulatory review projects for innovative drugs and regenerative medical products have been developed in the US, the EU, and Japan. Each regulatory agency has elaborated an original regulatory framework and adopted regulatory projects developed by the other regulatory agencies. For example, the Food and Drug Administration (FDA) first developed the breakthrough therapy designation, and then the Pharmaceuticals and Medical Devices Agency (PMDA) and European Medicines Agency (EMA) introduced the Sakigake designation and the priority medicines (PRIME) designation, respectively. In addition, the necessity of the product being first development in Japan is the original feature of the Sakigake designation, while actively supporting the development of advanced-therapy medicinal products (AMTPs) by academia or small/medium-sized sponsors is the original feature of the PRIME; these particular features are different from the breakthrough therapy designation in the US. In this review article, flexible and expedited review processes for new drugs, and cell and gene therapies in the US, the EU, and Japan are described. Moreover, all the drugs and regenerative medical products that were granted conditional approval or Sakigake designation in Japan are listed and analyzed herein.


Assuntos
Terapia Genética/tendências , Medicina Regenerativa/tendências , Terapias em Estudo/tendências , Europa (Continente)/epidemiologia , Órgãos Governamentais/tendências , Humanos , Japão/epidemiologia , Estados Unidos/epidemiologia , United States Food and Drug Administration
16.
Pediatr Rheumatol Online J ; 17(1): 56, 2019 Aug 20.
Artigo em Inglês | MEDLINE | ID: mdl-31429786

RESUMO

The idiopathic inflammatory myopathies (IIM) until recently have been considered a heterogeneous broad group of six autoimmune muscle diseases. Initially, autoantibodies in IIM (including JDM) and CD8+ T cell-induced cytotoxicity (PM and IBM) were the predominant recognized etiopathology mechanisms used to classify myopathies. In the early late 1990's to 2000's, evolving understanding of the molecules such as interleukin (IL), tumor necrosis factor (TNF), interferon (IFN), and other cytokines as well as differences in response to therapies, has led IIM researchers to look beyond previous disease mechanisms. For decades the overexpression of Th1- associated cytokines (TNF-α, IFN-γ and IL-12) in the areas of inflammation in skin and muscle in IIM pointed to Th1 as the primary pathway for inflammation in myositis.However, in the last decade overexpression and elevated level of Th17-associated cytokines (IL-17, IL-22, and IL-6) were identified in the blood and the inflamed muscles of myositis patients. We also do not know how Th1 and Th2 cytokines work differently in diverse hosts, in different concentrations, in different inflammatory milieus, and in the presence or absence of each other or other adhesion/co-stimulatory molecules such as NF-κB. Also, several autoantibodies to intracellular organelles have been identified in myositis.In this review, we will discuss the most recent advances in IIM research and how that might bring new biologic therapies to market in the next 5-15 years to assist in the care of our most difficult IIM and JDM patients.


Assuntos
Produtos Biológicos/uso terapêutico , Miosite/tratamento farmacológico , Adulto , Anticorpos Monoclonais Humanizados/uso terapêutico , Criança , Doença Crônica , Ensaios Clínicos como Assunto , Dermatomiosite/tratamento farmacológico , Previsões , Humanos , Imunossupressores/uso terapêutico , Terapias em Estudo/tendências
17.
Crit Rev Oncol Hematol ; 141: 139-145, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31295667

RESUMO

Primary central nervous system lymphoma (PCNSL) is a rare and aggressive form of diffuse large B-cell lymphoma. The frontline treatment with high-dose methotrexate based immunochemotherapy is not curative for the majority of patients. Gene expression profiling and next-generation sequencing have recently provided plethora of data shedding light on pathogenic mechanisms sustain PCNSL and identifying potential vulnerable mechanisms to be explored therapeutically. Here, we review established molecular drivers of PCNSL and targeted drugs that may change the current therapeutic paradigm.


Assuntos
Neoplasias do Sistema Nervoso Central/terapia , Terapia de Alvo Molecular , Medicina de Precisão/métodos , Medicina de Precisão/tendências , Terapias em Estudo , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias do Sistema Nervoso Central/diagnóstico , Neoplasias do Sistema Nervoso Central/genética , Neoplasias do Sistema Nervoso Central/patologia , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Imunoterapia/métodos , Imunoterapia/tendências , Linfoma Difuso de Grandes Células B/tratamento farmacológico , Linfoma não Hodgkin/tratamento farmacológico , Metotrexato/administração & dosagem , Terapia de Alvo Molecular/métodos , Terapia de Alvo Molecular/tendências , Terapias em Estudo/métodos , Terapias em Estudo/tendências
18.
Oncogene ; 38(34): 6159-6171, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31289361

RESUMO

Malignant tumors of the central nervous system (CNS) continue to be a leading cause of cancer-related mortality in both children and adults. Traditional therapies for malignant brain tumors consist of surgical resection and adjuvant chemoradiation; such approaches are often associated with extreme morbidity. Accordingly, novel, targeted therapeutics for neoplasms of the CNS, such as immunotherapy with oncolytic engineered herpes simplex virus (HSV) therapy, are urgently warranted. Herein, we discuss treatment challenges related to HSV virotherapy delivery, entry, replication, and spread, and in so doing focus on host anti-viral immune responses and the immune microenvironment. Strategies to overcome such challenges including viral re-engineering, modulation of the immunoregulatory microenvironment and combinatorial therapies with virotherapy, such as checkpoint inhibitors, radiation, and vaccination, are also examined in detail.


Assuntos
Neoplasias Encefálicas/terapia , Resistencia a Medicamentos Antineoplásicos , Herpesvirus Humano 1/fisiologia , Terapia Viral Oncolítica/métodos , Terapias em Estudo , Adulto , Neoplasias Encefálicas/genética , Criança , Resistencia a Medicamentos Antineoplásicos/imunologia , Terapia Genética/efeitos adversos , Terapia Genética/métodos , Vetores Genéticos , Humanos , Imunoterapia/efeitos adversos , Imunoterapia/métodos , Terapia Viral Oncolítica/efeitos adversos , Vírus Oncolíticos/fisiologia , Terapias em Estudo/métodos , Terapias em Estudo/tendências , Resultado do Tratamento
19.
Biol Aujourdhui ; 213(1-2): 59-64, 2019.
Artigo em Francês | MEDLINE | ID: mdl-31274104

RESUMO

The current treatment of migraine attacks is triptans and NSAIDs, but the calcitonin gene-related peptide (CGRP) has emerged as a key neuropeptide target for migraine therapy. Despite an off target class effect on liver enzymes, two CGRP receptor antagonists, ubrogepant and rimegepant, remain in development, together with a 5-HT1F receptor agonist (lasmiditan), for which cardiovascular contraindications that limit the utility of triptans do not exist. Importantly, to avoid an excessive use of acute medication with the risk of medication overuse, prophylactic therapeutics are the best choice. To date, monoclonal antibodies which block CGRP actions are on the market all over the world but not yet in France. The research is very active in different directions and targets notably hypothalamic neuropeptides because the hypothalamus hosts many key neuropeptide systems that seem to play a role in migraine physiopathology. These neuropeptides include orexins, oxytocin, neuropeptide Y (NPY) and pituitary adenylate cyclase-activating polypeptide (PACAP). In addition, other promising drugs for the treatment of migraine are nitric oxide synthase inhibitors and acid-sensing ion channel (ASIC) blockers.


Assuntos
Dor Crônica/terapia , Transtornos de Enxaqueca/prevenção & controle , Transtornos de Enxaqueca/terapia , Manejo da Dor/métodos , Terapias em Estudo/métodos , Doença Aguda , Analgésicos/uso terapêutico , Quimioprevenção/métodos , Quimioprevenção/tendências , Dor Crônica/epidemiologia , Drogas em Investigação/uso terapêutico , França/epidemiologia , Humanos , Transtornos de Enxaqueca/patologia , Manejo da Dor/tendências , Terapias em Estudo/tendências
20.
Ann Ist Super Sanita ; 55(2): 179-185, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31264641

RESUMO

BACKGROUND: Nowadays one of the most critical aspects of innovative cell-based therapies is the unregulated industry, as it is becoming a competitor of the regulated system. Many private clinics, worldwide, advertise and offer cell-based interventions treatments directly to the consumer and this poses a risk to both vulnerable patients and health systems. Several countries have implemented Compassionate Use Programmes (CUP) that provide patients with medicines that have not yet completed the approval pathway, in the event that no reasonable alternative exists. Recently, in the public discourse, compassionate use has been increasingly associated with a patient's right to try. Thus, the aim of this study was to assess public knowledge of the clinical trials process with specific reference to innovative stem cell treatments, and trust in the institutions responsible for regulatory activities. We also asked people about their "right" to use unregulated therapies. METHODS: We developed an ad hoc questionnaire on three main areas of concern and administered it to 300 people in the patient waiting room at an Italian university hospital. RESULTS: Our findings suggest that people have a good knowledge of the clinical trials process and trust in healthcare institutions. Nonetheless, one person in two believes it is a right to use unregulated therapies. CONCLUSIONS: We stress the need, in the age of cellular therapies, for a commitment to support vulnerable patients and to strengthen awareness among the public about the substantial boundary that differentiates experimental therapies from unproven therapies. There should not be a "right to try" something that is unsafe but rather approved treatments and in line with good clinical practice. The trend, which emerged on this issue from our study, is quite different, confirming the urgent need to improve health information so that it is as complete as possible.


Assuntos
Ensaios de Uso Compassivo , Direitos do Paciente , Direito à Saúde , Transplante de Células-Tronco , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Ensaios Clínicos como Assunto , Ensaios de Uso Compassivo/ética , Ensaios de Uso Compassivo/legislação & jurisprudência , Cultura , União Europeia , Feminino , Humanos , Itália , Masculino , Turismo Médico , Pessoa de Meia-Idade , Direitos do Paciente/ética , Direitos do Paciente/legislação & jurisprudência , Segurança do Paciente , Direito à Saúde/ética , Direito à Saúde/legislação & jurisprudência , Risco , Transplante de Células-Tronco/ética , Transplante de Células-Tronco/legislação & jurisprudência , Terapias em Estudo/ética , Confiança , Estados Unidos , Adulto Jovem
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