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Bioluminescence resonance energy transfer photodynamic therapy, which uses light generated by bioluminescent proteins to activate photosensitizers and produce reactive oxygen species without the need for external irradiation, has shown promising results in cancer models. However, the characterization of delivery systems that can incorporate the components of this therapy for preferential delivery to the tumor remains necessary. In this work, we have characterized parvovirus B19-like particles (B19V-VLPs) as a platform for a photosensitizer and a bioluminescent protein. By chemical and biorthogonal conjugation, we conjugated rose Bengal photosensitizer and firefly luciferase to B19V-VLPs and a protein for added specificity. The results showed that B19V-VLPs can withstand decoration with all three components without affecting its structure or stability. The conjugated luciferase showed activity and was able to activate rose Bengal to produce singlet oxygen without the need for external light. The photodynamic reaction generated by the functionalized VLPs-B19 can decrease the viability of tumor cells in vitro and affect tumor growth and metastasis in the 4 T1 model. Treatment with functionalized VLPs-B19 also increased the percentage of CD4 and CD8 cell populations in the spleen and in inguinal lymph nodes compared to vehicle-treated mice. Our results support B19V-VLPs as a delivery platform for bioluminescent photodynamic therapy components to solid tumors.
Assuntos
Fotoquimioterapia , Fármacos Fotossensibilizantes , Rosa Bengala , Animais , Fármacos Fotossensibilizantes/química , Fármacos Fotossensibilizantes/farmacologia , Fármacos Fotossensibilizantes/uso terapêutico , Camundongos , Rosa Bengala/química , Rosa Bengala/farmacologia , Rosa Bengala/uso terapêutico , Linhagem Celular Tumoral , Humanos , Oxigênio Singlete/metabolismo , Parvovirus B19 Humano/efeitos dos fármacos , Parvovirus B19 Humano/química , Neoplasias/tratamento farmacológico , Luciferases de Vaga-Lume/metabolismo , FemininoRESUMO
[This corrects the article DOI: 10.3389/fvets.2023.1187271.].
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The absence of tumor-infiltrating lymphocytes negatively impacts the response to chemotherapy and prognosis in all subtypes of breast cancer. Therapies that stimulate a proinflammatory environment may help improve the response to standard treatments and also to immunotherapies such as checkpoint inhibitors. Newcastle disease virus (NDV) shows oncolytic activity, as well as immune modulating potential, in the treatment of breast cancer in vitro and in vivo; however, its potential to enhance tumor-infiltrating immune cells in breast cancer has yet to be evaluated. Since spontaneous canine mammary tumors represent a translational model of human breast cancer, we conducted this proof-of-concept study, which could provide a rationale for further investigating NDV-MLS as immunotherapy for mammary cancer. Six female companion dogs with spontaneous mammary cancer received a single intravenous and intratumoral injection of oncolytic NDV-MLS. Immune cell infiltrates were evaluated by histology and immunohistochemistry in the stromal, intratumoral, and peritumoral compartments on day 6 after viral administration. Increasing numbers of immune cells were documented post-viral treatment, mainly in the peritumoral compartment, where plasma cells and CD3+ and CD3-/CD79- lymphocytes predominated. Viral administration was well tolerated, with no significant adverse events. These findings support additional research on the use of NDV-MLS immunotherapy for mammary cancer.
Assuntos
Neoplasias , Terapia Viral Oncolítica , Vírus Oncolíticos , Humanos , Animais , Feminino , Cães , Vírus da Doença de Newcastle/fisiologia , Animais de Estimação , Vírus Oncolíticos/fisiologia , Imunoterapia , Linhagem Celular Tumoral , Neoplasias/terapiaRESUMO
Breast cancer is the leading malignancy in women worldwide, both in terms of incidence and mortality. Triple-negative breast cancer (TNBC) is the type with the worst clinical outcomes and with fewer therapeutic options than other types of breast cancer. GK-1 is a peptide that in the experimental model of the metastatic 4T1 breast cancer has demonstrated anti-tumor and anti-metastatic properties. Herein, GK-1 (5 mg/kg, i.v.) weekly administrated not only decreases tumor growth and the number of lung macro-metastases but also lung and lymph nodes micro-metastases. Histological analysis reveals that GK-1 reduced 57% of the intra-tumor vascular areas, diminished the leukemoid reaction's progression, and the spleens' weight and length. A significant reduction in VEGF-C, SDF-1, angiopoietin-2, and endothelin-1 angiogenic factors was induced. Moreover, GK-1 prevents T cell exhaustion in the tumor-infiltrating lymphocytes (TILs) decreasing PD-1 expression. It also increased IFN-γ and granzyme-B expression and the cytotoxic activity of CD8+ TILs cells against tumor cells. All these features were found to be associated with a better antitumor response and prognosis. Altogether, these results reinforce the potential of GK-1 to improve the clinical outcome of triple-negative breast cancer immunotherapy. Translation research is ongoing towards its evaluation in humans.
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Antineoplásicos , Neoplasias de Mama Triplo Negativas , Humanos , Feminino , Animais , Camundongos , Neoplasias de Mama Triplo Negativas/patologia , Exaustão das Células T , Linfócitos do Interstício Tumoral/metabolismo , Prognóstico , Antineoplásicos/uso terapêutico , Linfócitos T CD8-Positivos/metabolismoRESUMO
Introduction: In veterinary medicine, cancer is the leading cause of death in companion animals, and mammary gland tumors represent the most common neoplasm in female dogs. Several epidemiological risk factors, such as age, breed, hormones, diet, and obesity have been reported to be relevant for canine mammary tumors. Nowadays, the gold standard for diagnosis of canine mammary tumors is the pathological examination of the suspected tissue. However, tumor grade can only be assessed after surgical removal or biopsy of the altered tissue. Therefore, in cases of tumors that could be surgically removed, it would be very helpful to be able to predict the biological behavior of the tumor, before performing any surgery. Since, inflammation constitutes part of the tumor microenvironment and it influences each step of tumorigenesis, cellular and biochemical blood markers of systemic inflammation, such as the neutrophil to lymphocyte ratio (NLR) and the albumin to globulin ratio (AGR) have been proposed as prognostic factors for human cancer development. The NLR and the AGR have not been explored enough as prognostic factors for cancer development in veterinary medicine. Methods: To determine the prognostic value of NLR in canine mammary tumors, clinical records including biochemistry and hematological studies of female dogs with mammary tumors and of control healthy dogs, were used to determine the pre-treatment NLR and AGR. Other clinical data included age, breed, tumor size, histological tumor grade, and survival time after surgery. Results and discussion: It was found that a higher pre-treatment NLR value (NLR > 5) associates with less survival rate. In contrast, the AGR did not show any predictive value on the malignancy of the tumor. However, by combining the NLR with AGR, age of the dog, and tumor size in a principal component analysis (PCA), the grade of the tumor and survival after surgery could be appropriately predicted. These data strongly suggest that pre-treatment NLR values have a prognostic value for the survival rate after surgery of dogs with mammary tumors.
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Use of the potent tyrosine kinase inhibitor imatinib as the first-line treatment in chronic myeloid leukemia (CML) has decreased mortality from 20% to 2%. Approximately 30% of CML patients experience imatinib resistance, however, largely because of point mutations in the kinase domain of the BCR-ABL1 fusion gene. The aim of this study was to use next-generation sequencing (NGS) to identify mutations related to imatinib resistance. The study included 22 patients diagnosed with CML and experiencing no clinical response to imatinib. Total RNA was used for cDNA synthesis, with amplification of a fragment encompassing the BCR-ABL1 kinase domain using a nested-PCR approach. Sanger and NGS were applied to detect genetic alterations. HaplotypeCaller was used for variant calling, and STAR-Fusion software was applied for fusion breakpoint identification. After sequencing analysis, F311I, F317L, and E450K mutations were detected respectively in three different participants, and in another two patients, single nucleotide variants in BCR (rs9608100, rs140506, rs16802) and ABL1 (rs35011138) were detected. Eleven patients carried e14a2 transcripts, nine had e13a2 transcripts, and both transcripts were identified in one patient. One patient had co-expression of e14a2 and e14a8 transcripts. The results identify candidate single nucleotide variants and co-expressed BCR-ABL1 transcripts in cellular resistance to imatinib.
Assuntos
Proteínas de Fusão bcr-abl , Leucemia Mielogênica Crônica BCR-ABL Positiva , Humanos , Mesilato de Imatinib/uso terapêutico , Proteínas de Fusão bcr-abl/genética , Leucemia Mielogênica Crônica BCR-ABL Positiva/tratamento farmacológico , Leucemia Mielogênica Crônica BCR-ABL Positiva/genética , Leucemia Mielogênica Crônica BCR-ABL Positiva/diagnóstico , Mutação , Inibidores de Proteínas Quinases/uso terapêutico , Nucleotídeos/uso terapêutico , Resistencia a Medicamentos Antineoplásicos/genéticaRESUMO
The objective was to understand the link between housing, health and quality of life in a context of social housing regeneration, through the experiences and perceptions of its inhabitants, exploring the mechanisms that sustain this link before regeneration, and those elements derived from housing regeneration that result in improvements in quality of life and potentially in health. Between 1980 and the 2000s, Chile faced a massive quantitative housing deficit through a policy that delivered more than 120,000 low-cost social housing apartments. Today, thousands present severe habitability problems, generating negative consequences for their inhabitants, their health and well-being. Seeking to solve the deterioration of housing and neighborhoods, the Chilean Ministry of Housing and Urbanism developed the Housing Complex Regeneration Program. The RUCAS project seeks to evaluate the effects of the program on health and to assess the impact of interventions such as these on vulnerable populations in Latin America. We present results of 8 interviews and 2 focus groups conducted in a social housing complex in process of intervention in Viña del Mar. Using discursive content analysis, results show that the poor material quality of housing is perceived as harmful to health. Regenerated housing, on the other hand, promotes the recovery and re-appropriation of spaces and their uses, sociability, new healthy practices, positive feelings and psychological well-being, bringing to the fore the psychosocial component of people's relationship with their house. It is concluded that housing regeneration has the potential to benefit physical and mental health through both direct mechanisms, derived from the renovated materiality, and indirect mechanisms related to the practices and experiences of the lived space.
El objetivo fue conocer el vínculo entre la vivienda, la salud y la calidad de vida en un contexto de regeneración de viviendas sociales, a partir de las experiencias y percepciones de sus habitantes, indagando en aquellos mecanismos que sostienen este vínculo antes de la regeneración, y en aquellos elementos derivados de la regeneración de la vivienda que se materializan en mejoras en la calidad de vida y potencialmente en la salud. Entre 1980 y los 2000, Chile enfrentó un masivo déficit cuantitativo de vivienda mediante una política que entregó más de 120.000 departamentos de vivienda social de bajo costo. Hoy en día, miles presentan severos problemas de habitabilidad, generando consecuencias negativas para sus habitantes, su salud y bienestar. Buscando dar solución al deterioro de la vivienda y el espacio público, el Ministerio de Vivienda y Urbanismo desarrolló el Programa de Regeneración de Conjuntos Habitacionales. El proyecto RUCAS busca evaluar los efectos del programa en la salud y evidenciar el impacto de intervenciones como éstas en poblaciones vulnerables en Latinoamérica. Se presentan resultados de 8 entrevistas y 2 grupos focales realizados en un conjunto de vivienda social en proceso de intervención en Viña del Mar. Usando análisis de contenido discursivo, los resultados muestran que la mala calidad material de la vivienda se percibe como dañino para la salud. La vivienda regenerada en tanto, promueve la recuperación y re-apropiación de los espacios y sus usos, la sociabilidad, nuevas prácticas saludables, sentimientos positivos y bienestar psicológico, emergiendo el componente psicosocial de la relación de las personas con su vivienda. Se concluye que la regeneración de la vivienda tiene el potencial de beneficiar a la salud física y mental por mecanismos tanto directos, devenidos de la materialidad renovada, como indirectos relacionados con las prácticas y experiencias en el espacio habitado.
O objetivo foi compreender a relação entre habitação, saúde e qualidade de vida em um contexto de regeneração da habitação social, com base nas experiências e percepções de seus habitantes, investigando aqueles mecanismos que sustentam esta relação antes da regeneração, e aqueles elementos derivados da regeneração que se materializam em melhorias na qualidade de vida e potencialmente na saúde. Entre 1980 e os anos 2000, o Chile enfrentou um enorme déficit habitacional quantitativo através de uma política que proporcionou mais de 120.000 moradias sociais de baixo custo. Hoje, milhares apresentam graves problemas de habitabilidade, gerando consequências negativas para seus habitantes, sua saúde e bem-estar. Em busca de uma solução para a deterioração da habitação e seus bairros, o Ministério da Habitação e Urbanismo do Chile desenvolveu o Programa de Regeneração Habitacional. O projeto RUCAS procura avaliar os efeitos do programa sobre a saúde e o impacto de tais intervenções sobre populações vulneráveis na América Latina. São apresentados os resultados de 8 entrevistas e 2 grupos focais realizados em um complexo habitacional social no processo de intervenção em Viña del Mar. Usando análise discursiva de conteúdo, os resultados mostram que a má qualidade do material da habitação é percebida como prejudicial à saúde. A moradia regenerada, por outro lado, promove a recuperação e reapropriação dos espaços e seus usos, a sociabilidade, novas práticas saudáveis, sentimentos positivos e bem-estar psicológico, emergindo o componente psicossocial da relação das pessoas com sua moradia. Conclui-se que a regeneração habitacional tem o potencial de beneficiar a saúde física e mental tanto através de mecanismos diretos, decorrentes da materialidade renovada, como de mecanismos indiretos relacionados às práticas e experiências no espaço vivido.
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Habitação Popular , Qualidade de Vida , Humanos , Brasil , Pesquisa Qualitativa , Bem-Estar PsicológicoRESUMO
BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causing coronavirus disease 2019 (COVID-19) is the most transmissible ß-coronavirus in history, affecting all population groups. Immunocompromised patients, particularly cancer patients, have been highlighted as a reservoir to promote accumulation of viral mutations throughout persistent infection. CASE PRESENTATION: We aimed to describe the clinical course and SARS-CoV-2 mutation profile for 102 days in an immunocompromised patient with non-Hodgkin's lymphoma and COVID-19. We used RT-qPCR to quantify SARS-CoV-2 viral load over time and whole-virus genome sequencing to identify viral lineage and mutation profile. The patient presented with a persistent infection through 102 days while being treated with cytotoxic chemotherapy for non-Hodgkin's lymphoma and received targeted therapy for COVID-19 with remdesivir and hyperimmune plasma. All sequenced samples belonged to the BA.1.1 lineage. We detected nine amino acid substitutions in five viral genes (Nucleocapsid, ORF1a, ORF1b, ORF13a, and ORF9b), grouped in two clusters: the first cluster with amino acid substitutions only detected on days 39 and 87 of sample collection, and the second cluster with amino acid substitutions only detected on day 95 of sample collection. The Spike gene remained unchanged in all samples. Viral load was dynamic but consistent with the disease flares. CONCLUSIONS: This report shows that the multiple mutations that occur in an immunocompromised patient with persistent COVID-19 could provide information regarding viral evolution and emergence of new SARS-CoV-2 variants.
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COVID-19 , Linfoma não Hodgkin , Humanos , SARS-CoV-2/genética , COVID-19/diagnóstico , Eliminação de Partículas Virais , Infecção Persistente , Linfoma não Hodgkin/complicações , Linfoma não Hodgkin/tratamento farmacológico , Hospedeiro ImunocomprometidoRESUMO
El objetivo fue conocer el vínculo entre la vivienda, la salud y la calidad de vida en un contexto de regeneración de viviendas sociales, a partir de las experiencias y percepciones de sus habitantes, indagando en aquellos mecanismos que sostienen este vínculo antes de la regeneración, y en aquellos elementos derivados de la regeneración de la vivienda que se materializan en mejoras en la calidad de vida y potencialmente en la salud. Entre 1980 y los 2000, Chile enfrentó un masivo déficit cuantitativo de vivienda mediante una política que entregó más de 120.000 departamentos de vivienda social de bajo costo. Hoy en día, miles presentan severos problemas de habitabilidad, generando consecuencias negativas para sus habitantes, su salud y bienestar. Buscando dar solución al deterioro de la vivienda y el espacio público, el Ministerio de Vivienda y Urbanismo desarrolló el Programa de Regeneración de Conjuntos Habitacionales. El proyecto RUCAS busca evaluar los efectos del programa en la salud y evidenciar el impacto de intervenciones como éstas en poblaciones vulnerables en Latinoamérica. Se presentan resultados de 8 entrevistas y 2 grupos focales realizados en un conjunto de vivienda social en proceso de intervención en Viña del Mar. Usando análisis de contenido discursivo, los resultados muestran que la mala calidad material de la vivienda se percibe como dañino para la salud. La vivienda regenerada en tanto, promueve la recuperación y re-apropiación de los espacios y sus usos, la sociabilidad, nuevas prácticas saludables, sentimientos positivos y bienestar psicológico, emergiendo el componente psicosocial de la relación de las personas con su vivienda. Se concluye que la regeneración de la vivienda tiene el potencial de beneficiar a la salud física y mental por mecanismos tanto directos, devenidos de la materialidad renovada, como indirectos relacionados con las prácticas y experiencias en el espacio habitado.
The objective was to understand the link between housing, health and quality of life in a context of social housing regeneration, through the experiences and perceptions of its inhabitants, exploring the mechanisms that sustain this link before regeneration, and those elements derived from housing regeneration that result in improvements in quality of life and potentially in health. Between 1980 and the 2000s, Chile faced a massive quantitative housing deficit through a policy that delivered more than 120,000 low-cost social housing apartments. Today, thousands present severe habitability problems, generating negative consequences for their inhabitants, their health and well-being. Seeking to solve the deterioration of housing and neighborhoods, the Chilean Ministry of Housing and Urbanism developed the Housing Complex Regeneration Program. The RUCAS project seeks to evaluate the effects of the program on health and to assess the impact of interventions such as these on vulnerable populations in Latin America. We present results of 8 interviews and 2 focus groups conducted in a social housing complex in process of intervention in Viña del Mar. Using discursive content analysis, results show that the poor material quality of housing is perceived as harmful to health. Regenerated housing, on the other hand, promotes the recovery and re-appropriation of spaces and their uses, sociability, new healthy practices, positive feelings and psychological well-being, bringing to the fore the psychosocial component of people's relationship with their house. It is concluded that housing regeneration has the potential to benefit physical and mental health through both direct mechanisms, derived from the renovated materiality, and indirect mechanisms related to the practices and experiences of the lived space.
O objetivo foi compreender a relação entre habitação, saúde e qualidade de vida em um contexto de regeneração da habitação social, com base nas experiências e percepções de seus habitantes, investigando aqueles mecanismos que sustentam esta relação antes da regeneração, e aqueles elementos derivados da regeneração que se materializam em melhorias na qualidade de vida e potencialmente na saúde. Entre 1980 e os anos 2000, o Chile enfrentou um enorme déficit habitacional quantitativo através de uma política que proporcionou mais de 120.000 moradias sociais de baixo custo. Hoje, milhares apresentam graves problemas de habitabilidade, gerando consequências negativas para seus habitantes, sua saúde e bem-estar. Em busca de uma solução para a deterioração da habitação e seus bairros, o Ministério da Habitação e Urbanismo do Chile desenvolveu o Programa de Regeneração Habitacional. O projeto RUCAS procura avaliar os efeitos do programa sobre a saúde e o impacto de tais intervenções sobre populações vulneráveis na América Latina. São apresentados os resultados de 8 entrevistas e 2 grupos focais realizados em um complexo habitacional social no processo de intervenção em Viña del Mar. Usando análise discursiva de conteúdo, os resultados mostram que a má qualidade do material da habitação é percebida como prejudicial à saúde. A moradia regenerada, por outro lado, promove a recuperação e reapropriação dos espaços e seus usos, a sociabilidade, novas práticas saudáveis, sentimentos positivos e bem-estar psicológico, emergindo o componente psicossocial da relação das pessoas com sua moradia. Conclui-se que a regeneração habitacional tem o potencial de beneficiar a saúde física e mental tanto através de mecanismos diretos, decorrentes da materialidade renovada, como de mecanismos indiretos relacionados às práticas e experiências no espaço vivido.
RESUMO
Background: Since its appearance, COVID-19 has immensely impacted our society. Public health measures, from the initial lockdowns to vaccination campaigns, have mitigated the crisis. However, SARS-CoV-2's persistence and evolving variants continue to pose global threats, increasing the risk of reinfections. Despite vaccination progress, understanding reinfections remains crucial for informed public health responses. Methods: We collected available data on clinical and genomic information for SARS-CoV-2 samples from patients treated in Mexico City from 2020 epidemiological week 10 to 2023 epidemiological week 06 encompassing the whole public health emergency's period. To identify clinical data we utilized the SISVER (Respiratory Disease Epidemiological Surveillance System) database for SARS-CoV-2 patients who received medical attention in Mexico City. For genomic surveillance we analyzed genomic data previously uploaded to GISAID generated by Mexican institutions. We used these data sources to generate descriptors of case number, hospitalization, death and reinfection rates, and viral variant prevalence throughout the pandemic period. Findings: The fraction of reinfected individuals in the COVID-19 infected population steadily increased as the pandemic progressed in Mexico City. Most reinfections occurred during the fifth wave (40%). This wave was characterized by the coexistence of multiple variants exceeding 80% prevalence; whereas all other waves showed a unique characteristic dominant variant (prevalence >95%). Shifts in symptom patient care type and severity were observed, 2.53% transitioned from hospitalized to ambulatory care type during reinfection and 0.597% showed the opposite behavior; also 7.23% showed a reduction in severity of symptoms and 6.05% displayed an increase in severity. Unvaccinated individuals accounted for the highest percentage of reinfections (41.6%), followed by vaccinated individuals (31.9%). Most reinfections occurred after the fourth wave, dominated by the Omicron variant; and after the vaccination campaign was already underway. Interpretation: Our analysis suggests reduced infection severity in reinfections, evident through shifts in symptom severity and care patterns. Unvaccinated individuals accounted for most reinfections. While our study centers on Mexico City, its findings may hold implications for broader regions, contributing insights into reinfection dynamics.