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1.
Semin Immunol ; 50: 101422, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-33262067

RESUMO

SARS-CoV-2, the virus that causes COVID-19, emerged in late 2019, and was declared a global pandemic on March 11th 2020. With over 50 million cases and 1.2 million deaths around the world, to date, this pandemic represents the gravest global health crisis of our times. Thus, the race to develop a COVID-19 vaccine is an urgent global imperative. At the time of writing, there are over 165 vaccine candidates being developed, with 33 in various stages of clinical testing. In this review, we discuss emerging insights about the human immune response to SARS-CoV-2, and their implications for vaccine design. We then review emerging knowledge of the immunogenicity of the numerous vaccine candidates that are currently being tested in the clinic and discuss the range of immune defense mechanisms that can be harnessed to develop novel vaccines that confer durable protection against SARS-CoV-2. Finally, we conclude with a discussion of the potential role of a systems vaccinology approach in accelerating the clinical testing of vaccines, to meet the urgent needs posed by the pandemic.


Assuntos
/imunologia , Desenho de Fármacos , Vacinologia/métodos , Adjuvantes Imunológicos/uso terapêutico , Adulto , Animais , Anticorpos Neutralizantes/imunologia , Anticorpos Antivirais/imunologia , /patologia , Modelos Animais de Doenças , Humanos , Pessoa de Meia-Idade , Biologia de Sistemas/métodos , Linfócitos T/imunologia , Adulto Jovem
2.
Med Hypotheses ; 144: 110202, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-33254510

RESUMO

Toll-like receptor 7 is critical in recognition of single strand RNA viruses, including SARS CoV-2, and generation of anti-viral immunity. Coronaviruses evolved strategies to dampen the host immunity. Herein, we discuss the potential use of TLR7 agonists in the early stages of COVID-19 treatment.


Assuntos
Antivirais/uso terapêutico , Imiquimode/uso terapêutico , Receptor 7 Toll-Like/agonistas , Adjuvantes Imunológicos/administração & dosagem , Adjuvantes Imunológicos/uso terapêutico , Antivirais/administração & dosagem , Humanos , Imiquimode/administração & dosagem , Imunidade Inata/efeitos dos fármacos , Modelos Imunológicos , Pandemias , Creme para a Pele
3.
Arch Esp Urol ; 73(10): 879-894, 2020 12.
Artigo em Espanhol | MEDLINE | ID: mdl-33269707

RESUMO

Therapeutic approaches for treatment of urothelial transitional cell carcinoma based on immune system modulation, as well as the contribution of intravesica Bacillus de Calmette-Guérin (BCG) and the recentin corporation of checkpoint inhibitors had found irrefutable proofs of concept for the indication of antitumoral immunontherapy in such tumors. Its extension and development at the present time covers all the locations of the wide spectrum of presentation and evolution of these tumors. Nowadays, apart for the low grade non muscle-invasive tumors, we are facingan unpredictable development of antitumoral immunotherapy in bladder cancer not only as an option in the primary treatment, but also in other scenarios such asnon-responders when it comes to BCG, or the situation of ineligibility for systemic chemotherapy indication. The main objective of this review article is trying to translate the current basic mechanisms involved in different phases of transitional cell carcinomas antitumoral response, regardless of whether they are muscle-invasive or not, and to establish the rationale for their therapeutic intravesical or systemic administration. The role of the interactions established between urothelial tumor cells and the cellular and molecular elements of the immune system of patients is described, incorporating the relevant and recent advances in immunobiology and the molecular characterization of these tumors thatwill undoubtedly introduce far-reaching modifications intherapeutic regimes that will contrast with the traditional options available. Investigational lines that are already active in the clinical research phase with BCG and, checkpoints inhibitors ofthe immune response are also analyzed, high lighting theneed to find predictive response markers as a real option for treatments personalization. The approach to the knowledge of the individual reactivity of the immune system of each patient as a determining factor to achieve it is proposed.


Assuntos
Carcinoma de Células de Transição , Neoplasias da Bexiga Urinária , Neoplasias Urológicas , Adjuvantes Imunológicos/uso terapêutico , Administração Intravesical , Vacina BCG/uso terapêutico , Carcinoma de Células de Transição/terapia , Humanos , Imunoterapia , Neoplasias da Bexiga Urinária/tratamento farmacológico
4.
Arch Esp Urol ; 73(10): 895-905, 2020 12.
Artigo em Espanhol | MEDLINE | ID: mdl-33269708

RESUMO

Bladder cancer was one of the first to have a successful treatment based on immune system stimulation, recognized by patient survival and tumor recurrence data. In addition, bladder tumors are now known to have high antigenic load and are therefore considered to be susceptible to respond well to new immunotherapies. For these reasons, studying the mechanism of action of bladder cancer immunological-based treatments can provide valuable information both to improve their current use and to under stand why they work in some patients while others do not tolerate this therapy or have tumor progression. In this article, we will focus on the immune response generated by treatment of non-muscle invasive bladder tumors with BCG, as well as the relationship between this knowledge and new immunotherapies. We will first describe the main activities of the immune system, to continue with the treatment of bladder cancer with BCG, its mechanism of action and biomarkers. Finally, we will summarize the observations that led to the useof monoclonal antibody immunotherapy in cancer and will describe some of the new immunotherapies in use to treat bladder cancer patients.


Assuntos
Neoplasias da Bexiga Urinária , Adjuvantes Imunológicos/uso terapêutico , Administração Intravesical , Vacina BCG/uso terapêutico , Biomarcadores , Humanos , Imunoterapia , Recidiva Local de Neoplasia , Neoplasias da Bexiga Urinária/tratamento farmacológico
5.
Arch Esp Urol ; 73(10): 918-928, 2020 12.
Artigo em Espanhol | MEDLINE | ID: mdl-33269710

RESUMO

Since its introduction more than 40 years ago, adjuvant treatment with BCG (Bacillus Calmette-Guérin) for non-muscle invasive bladder cancer (NMIBC) continues to be the treatment recommended in the highrisk group, and one of the most successful immunotherapies for cancer treatment. However, up to 20% of patients will progress to muscle-invasive disease after BCG treatment. On the other hand, we are facing a shortage of BCG supply worldwide. Despite its extensive clinical use, there is no clear certainty of the mechanism of action of BCG, and controversy persists regarding to the most effective dose and strains, as well as their usefulness in combined treatments with other drugs and with devices that could facilitate their action on the bladder. This article historically reviews the impact that has had BCG in the treatment of NMIBC, the current guidelines in terms of doses, strains and treatments combination, and the future that will happen with the results of the ongoing clinical trials with systemic immunotherapy, vaccines and gene therapy.


Assuntos
Vacina BCG , Neoplasias da Bexiga Urinária , Adjuvantes Imunológicos/uso terapêutico , Administração Intravesical , Vacina BCG/uso terapêutico , Terapia Combinada , Humanos , Imunoterapia , Neoplasias da Bexiga Urinária/tratamento farmacológico
6.
Arch Esp Urol ; 73(10): 929-933, 2020 12.
Artigo em Espanhol | MEDLINE | ID: mdl-33269711

RESUMO

BCG is currently the standard of care in intermediate and high risk non-invasive bladder tumors. In high-risk patients treated with BCG up to 30% will recurand 10% will progress within 2 years. Oncological outcomes with bladder preserving strategies are limited so radical cystectomy is recommended after BCG failure. Some promising treatments, such as check point inhibitors (PD1, PDL-1), are being studied for non-responders to BCG. Knowing the management of critical situations during BCG treatment its crucial in daily practice and clinical trials design. The aim of this study is to present these definitions and to remember some important aspect sof BCG management.


Assuntos
Vacina BCG , Neoplasias da Bexiga Urinária , Adjuvantes Imunológicos/uso terapêutico , Administração Intravesical , Vacina BCG/uso terapêutico , Cistectomia , Progressão da Doença , Humanos , Invasividade Neoplásica , Recidiva Local de Neoplasia , Neoplasias da Bexiga Urinária/cirurgia
7.
Semin Immunol ; 50: 101426, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-33257234

RESUMO

In the last decade there have been some significant advances in vaccine adjuvants, particularly in relation to their inclusion in licensed products. This was proceeded by several decades in which such advances were very scarce, or entirely absent, but several novel adjuvants have now been included in licensed products, including in the US. These advances have relied upon several key technological insights that have emerged in this time period, which have finally allowed an in depth understanding of how adjuvants work. These advances include developments in systems biology approaches which allow the hypotheses first advanced in pre-clinical studies to be critically evaluated in human studies. This review highlights these recent advances, both in relation to the adjuvants themselves, but also the technologies that have enabled their successes. Moreover, we critically appraise what will come next, both in terms of new adjuvant molecules, and the technologies needed to allow them to succeed. We confidently predict that additional adjuvants will emerge in the coming years that will reach approval in licensed products, but that the components might differ significantly from those which are currently used. Gradually, the natural products that were originally used to build adjuvants, since they were readily available at the time of initial development, will come to be replaced by synthetic or biosynthetic materials, with more appealing attributes, including more reliable and robust supply, along with reduced heterogeneity. The recent advance in vaccine adjuvants is timely, given the need to create novel vaccines to deal with the COVID-19 pandemic. Although, we must ensure that the rigorous safety evaluations that allowed the current adjuvants to advance are not 'short-changed' in the push for new vaccines to meet the global challenge as quickly as possible, we must not jeopardize what we have achieved, by pushing less established technologies too quickly, if the data does not fully support it.


Assuntos
Adjuvantes Imunológicos/uso terapêutico , /prevenção & controle , Compostos de Alúmen/farmacologia , /uso terapêutico , Humanos , Biologia de Sistemas , Vacinologia/métodos
8.
Sci Rep ; 10(1): 20085, 2020 11 18.
Artigo em Inglês | MEDLINE | ID: mdl-33208827

RESUMO

The COVID-19 pandemic is a worldwide health emergency which calls for an unprecedented race for vaccines and treatment. In developing a COVID-19 vaccine, we applied technology previously used for MERS-CoV to produce a prefusion-stabilized SARS-CoV-2 spike protein, S-2P. To enhance immunogenicity and mitigate the potential vaccine-induced immunopathology, CpG 1018, a Th1-biasing synthetic toll-like receptor 9 (TLR9) agonist was selected as an adjuvant candidate. S-2P in combination with CpG 1018 and aluminum hydroxide (alum) was found to be the most potent immunogen and induced high titer of neutralizing antibodies in sera of immunized mice against pseudotyped lentivirus reporter or live wild-type SARS-CoV-2. In addition, the antibodies elicited were able to cross-neutralize pseudovirus containing the spike protein of the D614G variant, indicating the potential for broad spectrum protection. A marked Th1 dominant response was noted from cytokines secreted by splenocytes of mice immunized with CpG 1018 and alum. No vaccine-related serious adverse effects were found in the dose-ranging study in rats administered single- or two-dose regimens of S-2P combined with CpG 1018 alone or CpG 1018 with alum. These data support continued development of CHO-derived S-2P formulated with CpG 1018 and alum as a candidate vaccine to prevent COVID-19 disease.


Assuntos
/imunologia , Imunogenicidade da Vacina , Glicoproteína da Espícula de Coronavírus/imunologia , Adjuvantes Imunológicos/uso terapêutico , Hidróxido de Alumínio/uso terapêutico , Animais , Anticorpos Neutralizantes/sangue , Anticorpos Neutralizantes/imunologia , Anticorpos Antivirais/sangue , Anticorpos Antivirais/imunologia , Células CHO , /uso terapêutico , Cricetinae , Cricetulus , Citocinas/sangue , Citocinas/metabolismo , Feminino , Células HEK293 , Humanos , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Oligodesoxirribonucleotídeos/uso terapêutico , Ratos , Ratos Sprague-Dawley , Baço/imunologia , Células Th1/imunologia
9.
Folia Biol (Praha) ; 66(3): 86-90, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33069187

RESUMO

Covid-19 or SARS-CoV-2, a new RNA virus with high infectivity, and seemingly low mutability, which appeared in 2019 in the Wuhan province of China, has created a pandemic with dire consequences. At the end of May 2020, it became the first cause of mortality. As no treatment or vaccine may become available before many months, and because occurrence of similar pandemics is only a matter of time, arguments are presented here for testing the effect of transfer factor (TF), an immunomodulator devoid of toxicity, which has been extensively studied in the past for the treatment and prevention of viral infections.


Assuntos
Infecções por Coronavirus/imunologia , Infecções por Coronavirus/terapia , Pneumonia Viral/imunologia , Pneumonia Viral/terapia , Fator de Transferência/uso terapêutico , Adjuvantes Imunológicos/uso terapêutico , Animais , Betacoronavirus , Humanos , Pandemias , Projetos de Pesquisa
10.
PLoS One ; 15(9): e0238476, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32877451

RESUMO

BACKGROUND: Relapsing-remitting multiple sclerosis (RRMM) is a chronic, progressive, inflammatory and immune-mediated disease that affects the central nervous system and is characterized by episodes of neurological dysfunction followed by a period of remission. The pharmacological strategy aims to delay the progression of the disease and prevent relapse. Interferon beta and glatiramer are commonly used in the Brazilian public health system and are available to patients who meet the guideline criteria. The scenario of multiple treatments available and in development brings the need for discussion and evaluation of the technologies already available before the incorporation of new drugs. This study analyses the effectiveness of first-line treatment of RRMS measured by real-world evidence data, from the Brazilian National Health System (SUS). METHODS AND FINDINGS: We conducted a non-concurrent national cohort between 2000 and 2015. The study population consisted of 22,722 patients with RRMS using one of the following first-line drugs of interest: glatiramer or one of three presentations of interferon beta. Kaplan-Meier analysis was used to estimate the time to treatment failure. A univariate and multivariate Cox proportional hazard model was used to evaluate factors associated with treatment failure. In addition, patients were propensity score-matched (1:1) in six groups of comparative first-line treatments to evaluate the effectiveness among them. The analysis indicated a higher risk of treatment failure in female patients (HR = 1.08; P = 0,01), those with comorbidities at baseline (HR = 1.20; P<0,0001), in patients who developed comorbidities after starting treatment (i.e., rheumatoid arthritis-HR = 1.65; P<0,0001), those exclusive SUS patients (HR = 1.31; P<0,0001) and among patients using intramuscular interferon beta (IM ßINF-1a) (28% to 60% compared to the other three treatments; P<0,0001). Lower risk of treatment failure was found among patients treated with glatiramer. CONCLUSIONS: This retrospective cohort suggests that glatiramer is associated with greater effectiveness compared to the three presentations of interferon beta. When evaluating beta interferons, the results suggest that the intramuscular presentation is not effective in the treatment of multiple sclerosis.


Assuntos
Esclerose Múltipla Recidivante-Remitente/tratamento farmacológico , Resultado do Tratamento , Adjuvantes Imunológicos/uso terapêutico , Adulto , Brasil/epidemiologia , Estudos de Coortes , Análise Custo-Benefício , Feminino , Acetato de Glatiramer/uso terapêutico , Humanos , Interferon beta/uso terapêutico , Estimativa de Kaplan-Meier , Masculino , Esclerose Múltipla/tratamento farmacológico , Modelos de Riscos Proporcionais , Estudos Retrospectivos
11.
Paediatr Respir Rev ; 36: 57-64, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32958428

RESUMO

The Bacille Calmette Guérin (BCG) vaccine was developed over a century ago and has become one of the most used vaccines without undergoing a modern vaccine development life cycle. Despite this, the vaccine has protected many millions from severe and disseminated forms of tuberculosis (TB). In addition, BCG has cross-mycobacterial effects against non-tuberculous mycobacteria and off-target (also called non-specific or heterologous) effects against other infections and diseases. More recently, BCG's effects on innate immunity suggest it might improve the immune response against viral respiratory infections including SARS-CoV-2. New TB vaccines, developed over the last 30 years, show promise, particularly in prevention of progression to disease from TB infection in young adults. The role of BCG in the context of new TB vaccines remains uncertain as most participants included in trials have been previously BCG immunised. BCG replacement vaccines are in efficacy trials and these may also have off-target effects.


Assuntos
Adjuvantes Imunológicos/uso terapêutico , Vacina BCG/uso terapêutico , Proteção Cruzada/imunologia , Imunidade Heteróloga/imunologia , Infecções por Mycobacterium não Tuberculosas/prevenção & controle , Vacinas contra a Tuberculose/uso terapêutico , Tuberculose/prevenção & controle , Vacina BCG/imunologia , Úlcera de Buruli/microbiologia , Úlcera de Buruli/prevenção & controle , Diabetes Mellitus Tipo 1/epidemiologia , Diabetes Mellitus Tipo 1/imunologia , Humanos , Hipersensibilidade/epidemiologia , Hipersensibilidade/imunologia , Lactente , Mortalidade Infantil , Hanseníase/microbiologia , Hanseníase/prevenção & controle , Infecções por Mycobacterium não Tuberculosas/microbiologia , Micobactérias não Tuberculosas/imunologia , Infecções Respiratórias/epidemiologia , Infecções Respiratórias/imunologia , Vacinas contra a Tuberculose/imunologia
12.
N Engl J Med ; 383(12): 1139-1148, 2020 09 17.
Artigo em Inglês | MEDLINE | ID: mdl-32877599

RESUMO

BACKGROUND: In the previously reported primary analysis of this phase 3 trial, 12 months of adjuvant dabrafenib plus trametinib resulted in significantly longer relapse-free survival than placebo in patients with resected stage III melanoma with BRAF V600E or V600K mutations. To confirm the stability of the relapse-free survival benefit, longer-term data were needed. METHODS: We randomly assigned 870 patients who had resected stage III melanoma with BRAF V600E or V600K mutations to receive 12 months of oral dabrafenib (at a dose of 150 mg twice daily) plus trametinib (2 mg once daily) or two matched placebos. The primary end point was relapse-free survival. Here, we report 5-year results for relapse-free survival and survival without distant metastasis as the site of the first relapse. Overall survival was not analyzed, since the required number of events to trigger the final overall survival analysis had not been reached. RESULTS: The minimum duration of follow-up was 59 months (median patient follow-up, 60 months for dabrafenib plus trametinib and 58 months for placebo). At 5 years, the percentage of patients who were alive without relapse was 52% (95% confidence interval [CI], 48 to 58) with dabrafenib plus trametinib and 36% (95% CI, 32 to 41) with placebo (hazard ratio for relapse or death, 0.51; 95% CI, 0.42 to 0.61). The percentage of patients who were alive without distant metastasis was 65% (95% CI, 61 to 71) with dabrafenib plus trametinib and 54% (95% CI, 49 to 60) with placebo (hazard ratio for distant metastasis or death, 0.55; 95% CI, 0.44 to 0.70). No clinically meaningful between-group difference in the incidence or severity of serious adverse events was reported during the follow-up period. CONCLUSIONS: In the 5-year follow-up of a phase 3 trial involving patients who had resected stage III melanoma with BRAF V600E or V600K mutations, 12 months of adjuvant therapy with dabrafenib plus trametinib resulted in a longer duration of survival without relapse or distant metastasis than placebo with no apparent long-term toxic effects. (Funded by GlaxoSmithKline and Novartis; COMBI-AD ClinicalTrials.gov number, NCT01682083; EudraCT number, 2012-001266-15.).


Assuntos
Adjuvantes Imunológicos/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Imidazóis/uso terapêutico , Melanoma/tratamento farmacológico , Oximas/uso terapêutico , Proteínas Proto-Oncogênicas B-raf/genética , Piridonas/uso terapêutico , Pirimidinonas/uso terapêutico , Neoplasias Cutâneas/tratamento farmacológico , Administração Oral , Adulto , Idoso , Intervalo Livre de Doença , Método Duplo-Cego , Feminino , Seguimentos , Humanos , Masculino , Melanoma/genética , Pessoa de Meia-Idade , Mutação , Metástase Neoplásica , Estadiamento de Neoplasias , Inibidores de Proteínas Quinases/uso terapêutico , Proteínas Proto-Oncogênicas B-raf/antagonistas & inibidores , Neoplasias Cutâneas/genética , Análise de Sobrevida
13.
Int Immunopharmacol ; 88: 106873, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32795897

RESUMO

BACKGROUND: COVID-19 characterized by refractory hypoxemia increases patient mortality because of immunosuppression effects. This study aimed to evaluate the efficacy of immunomodulatory with thymosin α1 for critical COVID-19 patients. METHODS: This multicenter retrospective cohort study was performed in 8 government-designated treatment centers for COVID-19 patients in China from Dec. 2019 to Mar. 2020. Thymosin α1 was administrated with 1.6 mg qd or q12 h for >5 days. The primary outcomes were the 28-day and 60-day mortality, the secondary outcomes were hospital length of stay and the total duration of the disease. Subgroup analysis was carried out according to clinical classification. RESULTS: Of the 334 enrolled COVID-19 patients, 42 (12.6%) died within 28 days, and 55 (16.5%) died within 60 days of hospitalization. There was a significant difference in the 28-day mortality between the thymosin α1 and non-thymosin α1-treated groups in adjusted model (P = 0.016), without obvious differences in the 60-day mortality and survival time in the overall cohort (P > 0.05). In the subgroup analysis, it was found that thymosin α1 therapy significantly reduced 28-day mortality (Hazards Ratios HR, 0.11, 95% confidence interval CI 0.02-0.63, P=0.013) via improvement of Pa02/FiO2 (P = 0.036) and prolonged the hospital length of stay (P = 0.024) as well as the total duration of the disease (P=0.001) in the critical type patients, especially those aged over 64 years, with white blood cell >6.8×109/L, neutrophil >5.3×109/L, lymphocyte < 0.73 × 109/L, PaO2/FiO2 < 196, SOFA > 3, and acute physiology and chronic health evaluation (APACHE) II > 7. CONCLUSION: These results suggest that treatment with thymosin α1 can markedly decrease 28-day mortality and attenuate acute lung injury in critical type COVID-19 patients.


Assuntos
Adjuvantes Imunológicos/uso terapêutico , Infecções por Coronavirus/tratamento farmacológico , Cuidados Críticos/métodos , Pneumonia Viral/tratamento farmacológico , Timalfasina/uso terapêutico , APACHE , Adjuvantes Imunológicos/administração & dosagem , Adjuvantes Imunológicos/efeitos adversos , Idoso , Betacoronavirus , China/epidemiologia , Estudos de Coortes , Infecções por Coronavirus/imunologia , Infecções por Coronavirus/mortalidade , Estado Terminal , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Mortalidade/tendências , Pandemias , Pneumonia Viral/imunologia , Pneumonia Viral/mortalidade , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Timalfasina/administração & dosagem , Timalfasina/efeitos adversos
14.
Am J Trop Med Hyg ; 103(5): 1852-1854, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-32815507

RESUMO

Chromoblastomycosis is a cutaneous fungal infection caused by dematiaceous fungi that belong to the order Chaetothyriales and family Herpotrichiellaceae. This infection is prevalent in tropical and subtropical areas and has been designated as a neglected tropical disease according to the WHO. Chromoblastomycosis infection is difficult to treat, and there are limited therapeutic options, making urgent the characterization of new medicines or approaches to treat such infection. In the present case report, two patients with extensive chromoblastomycosis lesions were treated with the combination of itraconazole, acitretin, and imiquimod. In the fourth month of treatment, both patients showed improvement of verrucous plates, suggesting that acitretin combined with drugs already used in chromoblastomycosis therapy can decrease the time of treatment, improving patient's quality of life.


Assuntos
Acitretina/uso terapêutico , Cromoblastomicose/tratamento farmacológico , Cromoblastomicose/patologia , Imiquimode/uso terapêutico , Itraconazol/uso terapêutico , Acitretina/administração & dosagem , Adjuvantes Imunológicos/administração & dosagem , Adjuvantes Imunológicos/uso terapêutico , Antifúngicos/administração & dosagem , Antifúngicos/uso terapêutico , Quimioterapia Combinada , Humanos , Imiquimode/administração & dosagem , Itraconazol/administração & dosagem , Ceratolíticos/administração & dosagem , Ceratolíticos/uso terapêutico , Masculino , Pessoa de Meia-Idade
16.
Bull Cancer ; 107(5S): S49-S55, 2020 Jun.
Artigo em Francês | MEDLINE | ID: mdl-32620207

RESUMO

Local and systemic immunotherapies are used for the management of bladder cancer in daily practice. BCG has been administered for almost 40 years in patients with non-muscle invasive bladder cancer (NMIBC). Despite its efficacy, disease progression is observed in nearly 30% of patients. Given the antitumor activity of immune checkpoint inhibitors in metastatic setting, these therapies are currently investigated in NMIBC. Pembrolizumab is now approved by the Food and Drug Administration (FDA) for the treatment of patients with BCG-unresponsive, high-risk, NMIBC with carcinoma in situ with or without papillary tumors who are ineligible for or have not elected to undergo cystectomy. Several phase 3 trials are ongoing to investigate the efficacy of PD(L)1 inhibitors combined with BCG such as ALBAN study in France.


Assuntos
Imunoterapia , Neoplasias da Bexiga Urinária/terapia , Adjuvantes Imunológicos/uso terapêutico , Administração Intravesical , Anticorpos Monoclonais Humanizados/uso terapêutico , Antineoplásicos/uso terapêutico , Vacina BCG/uso terapêutico , Humanos , Invasividade Neoplásica , Nivolumabe/uso terapêutico , Neoplasias da Bexiga Urinária/patologia
17.
Tohoku J Exp Med ; 251(3): 175-181, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32641644

RESUMO

The novel coronavirus disease 2019 (COVID-19) is now officially declared as a pandemic by the World Health Organization (WHO), and most parts of the world are taking drastic measures to restrict human movements to contain the infection. Millions around the world are wondering, if there is anything that could be done, other than maintaining high personal hygiene, and be vigilant of the symptoms, to reduce the spread of the disease and chances of getting infected, or at least to lessen the burden of the disease, caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The National and International health agencies, including the National Institutes of Health (NIH), the Centers for Disease Control and Prevention (CDC), and the WHO have provided clear guidelines for both preventive and treatment suggestions. In this article, I will briefly discuss, why keeping adequate zinc balance might enhance the host response and be protective of viral infections.


Assuntos
Betacoronavirus , Infecções por Coronavirus/prevenção & controle , Pandemias/prevenção & controle , Pneumonia Viral/prevenção & controle , Zinco/fisiologia , Adjuvantes Imunológicos/farmacologia , Adjuvantes Imunológicos/uso terapêutico , Fatores Etários , Animais , Antivirais/farmacologia , Antivirais/uso terapêutico , Betacoronavirus/efeitos dos fármacos , Betacoronavirus/fisiologia , Infecções por Coronavirus/tratamento farmacológico , Infecções por Coronavirus/imunologia , Suplementos Nutricionais , Resistência à Doença/efeitos dos fármacos , Relação Dose-Resposta a Droga , Humanos , Sistema Imunitário/efeitos dos fármacos , Micronutrientes/fisiologia , Pneumonia Viral/tratamento farmacológico , Pneumonia Viral/imunologia , Replicação Viral/efeitos dos fármacos , Zinco/administração & dosagem , Zinco/deficiência , Zinco/farmacologia
18.
Braz J Med Biol Res ; 53(8): e9886, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32609262

RESUMO

The objective of this study was to compare the safety and efficacy of 0.2% hyaluronic acid (HA) topical gel and dexamethasone topical ointment in the treatment of recurrent aphthous ulcers (RAU) in children. This retrospective observational study included 104 patients who had more than two episodes of oral aphthous ulcers per year and were treated with HA (n=52) or dexamethasone (n=52) from August 15, 2014 to September 3, 2018. Therapy efficacy was evaluated based on the ulcer size and pain score before versus 7 days after either therapy. The paired t-test, chi-squared test, and independent t-test were utilized for statistical analyses. There was no significant difference in ulcer size or pain score between the HA and dexamethasone groups, on day 1 or day 7. Both treatments were tolerated well and no side effects were reported. No significant differences in body temperature, respiration rate, pulse, or systolic/diastolic blood pressure were observed between the start (day 1) and end of treatment (day 7), for either treatment. HA and dexamethasone showed similar efficacy in reducing ulcer size and pain scores, and were tolerated equally well in children with RAU. Future high-quality studies with larger numbers of patients are needed to confirm our findings.


Assuntos
Adjuvantes Imunológicos/uso terapêutico , Anti-Inflamatórios/uso terapêutico , Dexametasona/uso terapêutico , Ácido Hialurônico/uso terapêutico , Estomatite Aftosa/tratamento farmacológico , Criança , Feminino , Humanos , Masculino , Dor , Recidiva , Estudos Retrospectivos
19.
Eur J Pharmacol ; 882: 173328, 2020 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-32603692

RESUMO

The novel coronavirus, later identified as SARS-CoV-2, originating from Wuhan in China in November 2019, quickly spread around the world becoming a pandemic. Despite the knowledge of previous coronaviruses, such as those responsible for the SARS and MERS-CoV epidemic, there is no drug or prophylaxis treatment to this day. The rapid succession of scientific findings on SARS-CoV-2 provides a significant number of potential drug targets. Nevertheless, at the same time, the high quantity of clinical data, generated by a large number of rapidly infected people, require accurate tests regarding effective medical treatments. Several in vitro and in vivo studies were rapidly initiated after the outbreak of the pandemic COVID-19. Initial clinical studies revealed the promising potential of remdesivir that demonstrated a powerful and specific in vitro antiviral activity for COVID-19. Promising effects appear to be attributable to hydroxychloroquine. Remdesivir and hydroxychloroquine are being tested in ongoing randomized trials. In contrast, oseltamivir was not effective and corticosteroids are not currently recommended. However, few data from ongoing clinical trials are identifying low molecular weight heparins, innate immune system stimulating agents, and inflammatory modulating agents as potential effective agents. The authors assume that the current pandemic will determine the need for a systematic approach based on big data analysis for identifying effective drugs to defeat SARS-Cov-2. This work is aimed to be a general reference point and to provide an overview as comprehensive as possible regarding the main clinical trials in progress at the moment.


Assuntos
Adjuvantes Imunológicos/farmacologia , Antivirais/farmacologia , Betacoronavirus/efeitos dos fármacos , Infecções por Coronavirus/tratamento farmacológico , Mediadores da Inflamação/farmacologia , Pneumonia Viral/tratamento farmacológico , Monofosfato de Adenosina/análogos & derivados , Monofosfato de Adenosina/farmacologia , Monofosfato de Adenosina/uso terapêutico , Adjuvantes Imunológicos/uso terapêutico , Alanina/análogos & derivados , Alanina/farmacologia , Alanina/uso terapêutico , Antivirais/uso terapêutico , Betacoronavirus/imunologia , Betacoronavirus/patogenicidade , Ensaios Clínicos como Assunto , Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/virologia , Glucocorticoides/farmacologia , Glucocorticoides/uso terapêutico , Heparina de Baixo Peso Molecular/farmacologia , Heparina de Baixo Peso Molecular/uso terapêutico , Humanos , Hidroxicloroquina/farmacologia , Hidroxicloroquina/uso terapêutico , Imunidade Inata/efeitos dos fármacos , Mediadores da Inflamação/uso terapêutico , Oseltamivir/farmacologia , Oseltamivir/uso terapêutico , Pandemias , Pneumonia Viral/epidemiologia , Pneumonia Viral/virologia , Resultado do Tratamento
20.
Eur J Pharmacol ; 882: 173329, 2020 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-32615182

RESUMO

Coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is a newly discovered highly pathogenic virus that was declared pandemic in March 2020 by the World Health Organization. The virus affects the respiratory system, produces an inflammatory storm that causes lung damage and respiratory dysfunction. It infects humans of all ages. The Covid-19 takes a more severe course in individuals with chronic metabolic diseases such as obesity, diabetes mellitus, and hypertension. This category of persons exhibits weak immune activity and decreased levels of endogenous antioxidants. Melatonin is a multifunctional signaling hormone synthesized and secreted primarily by the pineal gland. It is a potent antioxidant with immunomodulatory action and has remarkable anti-inflammatory effects under a variety of circumstances. Regarding Covid-19 and metabolic syndrome, adequate information about the relationship between these two comorbidities is required for better management of these patients. Since Covid-19 infection and complications involve severe inflammation and oxidative stress in people with obesity and diabetes, we anticipated the inclusion of melatonin, as powerful antioxidant, within proposed treatment protocols. In this context, melatonin is a potential and promising agent to help overcome Covid-19 infection and boost the immune system in healthy persons and obese and diabetic patients. This review summarizes some evidence from recently published reports on the utility of melatonin as a potential adjuvant in Covid-19-infected individuals with diabetes and obesity.


Assuntos
Betacoronavirus/imunologia , Infecções por Coronavirus/tratamento farmacológico , Diabetes Mellitus/imunologia , Melatonina/farmacologia , Obesidade/imunologia , Pneumonia Viral/tratamento farmacológico , Adjuvantes Imunológicos/farmacologia , Adjuvantes Imunológicos/uso terapêutico , Antioxidantes/farmacologia , Antioxidantes/uso terapêutico , Antivirais/farmacologia , Antivirais/uso terapêutico , Betacoronavirus/patogenicidade , Ensaios Clínicos como Assunto , Comorbidade , Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/imunologia , Infecções por Coronavirus/virologia , Diabetes Mellitus/epidemiologia , Interações entre Hospedeiro e Microrganismos/efeitos dos fármacos , Interações entre Hospedeiro e Microrganismos/imunologia , Humanos , Sistema Imunitário/efeitos dos fármacos , Pulmão , Melatonina/uso terapêutico , Obesidade/epidemiologia , Estresse Oxidativo/efeitos dos fármacos , Estresse Oxidativo/imunologia , Pandemias , Pneumonia Viral/epidemiologia , Pneumonia Viral/imunologia , Pneumonia Viral/virologia , Fatores de Risco , Resultado do Tratamento
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