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Cellular immunotherapy has revolutionized the oncology field, yielding improved results against hematological and solid malignancies. NK cells have become an attractive alternative due to their capacity to activate upon recognition of "stress" or "danger" signals independently of Major Histocompatibility Complex (MHC) engagement, thus making tumor cells a perfect target for NK cell-mediated cancer immunotherapy even as an allogeneic solution. While this allogeneic use is currently favored, the existence of a characterized memory function for NK cells ("memory-like" NK cells) advocates for an autologous approach, that would benefit from the allogeneic setting discoveries, but with added persistence and specificity. Still, both approaches struggle to exert a sustained and high anticancer effect in-vivo due to the immunosuppressive tumor micro-environment and the logistical challenges of cGMP production or clinical deployment. Novel approaches focused on the quality enhancement and the consistent large-scale production of highly activated therapeutic memory-like NK cells have yielded encouraging but still unconclusive results. This review provides an overview of NK biology as it relates to cancer immunotherapy and the challenge presented by solid tumors for therapeutic NKs. After contrasting the autologous and allogeneic NK approaches for solid cancer immunotherapy, this work will present the current scientific focus for the production of highly persistent and cytotoxic memory-like NK cells as well as the current issues with production methods as they apply to stress-sensitive immune cells. In conclusion, autologous NK cells for cancer immunotherapy appears to be a prime alternative for front line therapeutics but to be successful, it will be critical to establish comprehensives infrastructures allowing the production of extremely potent NK cells while constraining costs of production.
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Imunoterapia , Neoplasias , Humanos , Neoplasias/terapia , Células Matadoras Naturais , Microambiente TumoralRESUMO
OBJECTIVE: Great success has been achieved in CAR-T cell immunotherapy in the treatment of hematological tumors. However, it is particularly difficult in solid tumors, because CAR-T is difficult to enter interior and exert long-term stable immune effects. Dendritic cells (DCs) can not only present tumor antigens but also promote the infiltration of T cells. Therefore, CAR-T cells with the help of DC vaccines are a reliable approach to treat solid tumors. METHODS: To test whether DC vaccine could promote CAR-T cell therapy in solid tumors, DC vaccine was co-cultured with MSLN CAR-T cells. The in vitro effects of DC vaccine on CAR-T were assessed by measuring cell proliferation, cell differentiation, and cytokine secretion. Effects of DC vaccine on CAR-T were evaluated using mice with subcutaneous tumors in vivo. The infiltration of CAR-T was analyzed using immunofluorescence. The persistence of CAR-T in mouse blood was analyzed using real-time quantitative PCR. RESULTS: The results showed that DC vaccine significantly enhanced the proliferation potential of MSLN CAR-T cells in vitro. DC vaccines not only promoted the infiltration of CAR-T cells, but also significantly improved the persistence of CAR-T in solid tumors in vivo. CONCLUSION: In conclusion, this study has demonstrated that DC vaccine can promote CAR-T therapy in solid tumors, which provides the possibility of widespread clinical application of CAR-T cells in the future.
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Neoplasias , Receptores de Antígenos Quiméricos , Vacinas , Camundongos , Animais , Linfócitos T , Exaustão das Células T , Neoplasias/terapia , Imunoterapia Adotiva/métodosRESUMO
Oral colonization and infection by Candida species are common in cancer patients receiving chemoradiotherapy, which has significantly increased in recent years. This study aimed to evaluate the frequency, distribution, and antifungal susceptibility profiles of Candida species isolates in patients with hematological malignancy and solid tumors. This study was conducted on a total of 45 cancer patients undergoing treatment with concurrent chemoradiotherapy within 2019-2020. The identification of Candida species was accomplished based on conventional examination and molecular assays. The minimum inhibitory concentrations were determined based on the guidelines of Clinical and Laboratory Standards Institute. The highest prevalence rates of oral candidiasis were observed in patients with chronic lymphoid leukemia (24.4%) and lymphoma (20%). The majority of the patients had oral candidiasis caused by non-albicans Candida species (64.4%). The results of the multiplex PCR for the identification of Candida glabrata, Candida nivariensis, Candida bracarensis, and species-specific Candida parapsilosis complex showed that all isolate amplification products at 397 bp and 171 bp were related to C. glabrata and C. parapsilosis, respectively. There was a significant difference in the Candida species distribution between the hematological malignancies and solid tumors patients. The results of MIC showed that clotrimazole, voriconazole, and caspofungin were the most effective antifungal drugs against oral non-Candida albicans isolates. An understanding of the epidemiology of oral candidiasis among hematological malignancies and solid tumors patients is currently imperative to guide optimal empirical treatment strategies for affected patients.
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Candidíase Bucal , Neoplasias Hematológicas , Neoplasias , Humanos , Candidíase Bucal/microbiologia , Antifúngicos/farmacologia , Candida , Candida glabrata , Candida parapsilosis , Neoplasias Hematológicas/tratamento farmacológico , Testes de Sensibilidade Microbiana , Farmacorresistência FúngicaRESUMO
PURPOSE: In the last few decades, interest in palliative care and advance care planning has grown in Brazil and worldwide. Empirical studies are needed to reduce therapeutic obstinacy and medical futility in the end-of-life care of children with incurable cancer. The aim of this study was to investigate the effects of do-not-resuscitate-like (DNRL) orders on the quality of end-of-life care of children with incurable solid tumors at a cancer center in Brazil. METHODS: A retrospective observational cohort study of 181 pediatric patients with solid tumors followed at the Pediatric Oncology Department of the Brazilian National Cancer Institute, Rio de Janeiro, Brazil, who died due to disease progression from 2009 to 2013. Medical records were reviewed for indicators of quality of end-of-life care, including overtreatment, care planning, and care at death, in addition to documentation of the diagnosis of life-limiting illness and the presence of a DNRL order. Data were summarized using descriptive statistics. Univariate and multivariate logistic regression analyses were used to examine associations between demographics, disease, treatment, and indicators of end-of-life care with a DNRL order. RESULTS: A documented DNRL order was associated with lower odds of dying in the intensive care unit or emergency room (80%), dying within 30 days of endotracheal tube placement (80%), or cardiopulmonary resuscitation (CPR) administration at the time of death (96%). CONCLUSION: Placement of DNRL orders early in the disease process is critical in reducing futile treatment in pediatric patients with incurable cancer.
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Neoplasias , Assistência Terminal , Brasil , Criança , Humanos , Neoplasias/terapia , Cuidados Paliativos , Ordens quanto à Conduta (Ética Médica) , Estudos RetrospectivosRESUMO
BACKGROUND & AIMS: Cancer influences body composition, including a loss of muscle mass (MM), associated with worse outcomes. The study aimed to evaluate the agreement between MM estimated by calf circumference (CC) and computed tomography (CT) image as a reference method. METHODS: A cross-sectional study including patients (>20 years) diagnosed with cancer attending a reference center of oncology. Spearman's correlation was performed to verify the correlation between CC and MM by CT, including skeletal muscle area - SMA and skeletal muscle index - SMI. ROC curves, Kappa coefficient, sensitivity, specificity, positive and negative predictive values were obtained. RESULTS: The study included 219 patients, age 62.9 ± 13.1 years (mean ± standard deviation). Low CC was observed in 43.8% of the patients, and 29.2% had low SMI. CC positively correlated with SMA (rho = 0.333) and SMI (rho = 0.329), and fair agreements (K = 0.268) were observed between CC and SMI, with higher and significant values for males (K = 0.332) and patients below 60 years (K = 0.419). The area under the curve (AUC) for low CC to identifying low SMI was equal to 0.685 (CI 95% 0.606-0.765). Low CC presented fair agreement to identify low SMI in the sample; however, the negative predictive value was almost 80% for all analyses. CONCLUSIONS: Low CC is not a surrogate for low SMI in patients with cancer, but it could be an alternative, non-invasive, easy-to-perform method to pre-screen patients with cancer with adequate SMI.
Assuntos
Neoplasias , Sarcopenia , Idoso , Estudos Transversais , Humanos , Masculino , Pessoa de Meia-Idade , Músculo Esquelético/patologia , Neoplasias/complicações , Sarcopenia/complicações , Tomografia Computadorizada por Raios XRESUMO
SUMMARY: Cancer known as a malignant tumor, is a class of diseases involving abnormal cell growth with the potential to invade or spread to other parts of the body. The Ehrlich tumor is a mammary adenocarcinoma of mice developed in solid and ascitic forms. This study was aimed to investigate the effects of paclitaxel on Netrin 1 and Factor 8 expression and also in tumor cell proliferation, apoptosis, angiogenesis, and development of tumor in Ehrlich solid tumors treated with paclitaxel. In this study, 26 adult Balb/C male mice were used. 6 of them were used as stock. Ehrlich ascites cells taken from animals in stock were injected subcutaneously from the neck area to all animals. The mice were randomly assigned to two groups of ten rats per group. Paclitaxel treatment group 10 mg/kg were administered to mice intraperitoneally (i.p.) 4,9, and 14th days. 15th day the animals were sacrificed and tumor tissues were taken. Paraffin-embedded solid tumor sections were stained Hematoxylin & Eosin, Masson's Trichrome. Also solid tumor sections were stained immunohistochemically with Netrin1 and Factor 8. Tunel method was applied to determine apoptosis. Paclitaxel applied as a therapeutic Ehrlich solid tumor reduced the volume of tumors in the treatment groups. At the end of the experiments, in the treatment groups' significantly reduced the Netrin 1 expression and microvessel density compared to the group control. Also paclitaxel in the treatment group increased the number of apoptotic cells. We suggest that decreasing the expression of Netrin 1 would be reduced vessel density and increased apoptosis.
RESUMEN: El cáncer, conocido como tumor maligno, es una clase de enfermedad que involucra un crecimiento celular anormal con potencial de invadir o diseminarse a otras partes del cuerpo. El tumor de Ehrlich es un adenocarcinoma mamario de ratones desarrollado en formas sólidas y ascíticas. Este estudio tuvo como objetivo investigar los efectos del paclitaxel en la expresión de Netrin 1 y Factor 8 y también en la proliferación de células tumorales, apoptosis, angiogénesis y desarrollo de tumores sólidos de Ehrlich tratados con paclitaxel. En esta investigación se utilizaron 26 ratones machos Balb / C adultos. Seis de ellos se utilizaron como stock. Se inyectaron por vía subcutánea células de ascitis de Ehrlich tomadas de animales en la zona del cuello. Los ratones se asignaron aleatoriamente a dos grupos de diez ratas por grupo. Se administraron 10 mg/kg del grupo de tratamiento con paclitaxel a ratones por vía intraperitoneal (i.p.) 4, 9 y 14 días. El día 15 se sacrificaron los animales y se extrajeron los tejidos tumorales. Las secciones de tumor sólido incluidas en parafina se tiñeron con hematoxilina y eosina y tricrómico de Masson. También se tiñeron inmunohisto-químicamente secciones de tumor sólido con Netrin1 y Factor 8. Se aplicó el método Tunel para determinar la apoptosis. El paclitaxel aplicado como tumor sólido terapéutico de Ehrlich redujo el volumen de tumores en los grupos de tratamiento. Al final de los experimentos, en los grupos de tratamiento se redujo significativamente la expresión de Netrin 1 y la densidad de microvasos en comparación con el grupo control. Además, el paclitaxel en el grupo tratamiento aumentó el número de células apoptóticas. Sugerimos que la disminución de la expresión de Netrin 1 reduciría la densidad de los vasos y aumentaría la apoptosis.
Assuntos
Animais , Masculino , Camundongos , Carcinoma de Ehrlich/tratamento farmacológico , Paclitaxel/administração & dosagem , Netrina-1/antagonistas & inibidores , Antineoplásicos Fitogênicos/administração & dosagem , Fator VIII , Imuno-Histoquímica , Paclitaxel/farmacologia , Apoptose , Proliferação de Células/efeitos dos fármacos , Densidade Microvascular/efeitos dos fármacos , Camundongos Endogâmicos BALB C , Neovascularização Patológica , Antineoplásicos Fitogênicos/farmacologiaRESUMO
Pancreatic Ductal Adenocarcinoma (PDA) is a highly metastatic tumor, and the liver is its first target, which restricts the use of medications. PDA is considered one of the most aggressive types of cancer in the world, with an extremely short survival time, depending on the stage of diagnosis. In non-surgical cases, chemotherapy alternatives are only effective in 40% to 60% of patients. The low efficiency of treatments occurs mainly due to the complex microenvironment in PDA, leading to chemoresistance to treatments and making it difficult to reach the affected tissue. A very important histological characteristic of PDA is the extremely dense stroma, which leads to low vascularization of tumor tissue. Consequently, the stroma environment causes less drug accumulation in tumor cells, even of selective and/or targeted drugs. Overcoming the stroma's microenvironment is a major challenge for therapies. Moreover, specific genes lead to direct chemoresistance in PDA due to their high progression. In this scenario, nanotechnology appears as an alternative to overcome these clinical challenges concerning two distinct ways: acting on the stroma or/and acting directly on the pancreatic tumor cells. Thus, this review aimed to highlight advances in the application of nanotechnology aiming to open up new landscapes against PDA. There are a huge number of nanoparticles carrying drugs in preclinical and clinical trials for the effective treatment of PDA. These works have been discussed, and based on the current scenario, the future prospects for an efficient treatment of PDA have been proposed.
Assuntos
Carcinoma Ductal Pancreático , Neoplasias Pancreáticas , Carcinoma Ductal Pancreático/tratamento farmacológico , Sistemas de Liberação de Medicamentos , Humanos , Pâncreas , Neoplasias Pancreáticas/tratamento farmacológico , Microambiente TumoralRESUMO
Chimeric antigen receptor (CAR) engineering for T cells and natural killer cells (NK) are now under clinical evaluation for the treatment of hematologic cancers. Although encouraging clinical results have been reported for hematologic diseases, pre-clinical studies in solid tumors have failed to prove the same effectiveness. Thus, there is a growing interest of the scientific community to find other immune cell candidate to express CAR for the treatment of solid tumors and other diseases. Mononuclear phagocytes may be the most adapted group of cells with potential to overcome the dense barrier imposed by solid tumors. In addition, intrinsic features of these cells, such as migration, phagocytic capability, release of soluble factors and adaptive immunity activation, could be further explored along with gene therapy approaches. Here, we discuss the elements that constitute the tumor microenvironment, the features and advantages of these cell subtypes and the latest studies using CAR-myeloid immune cells in solid tumor models.
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Flavonoids have been proposed as potential chemotherapeutic agents because they are toxic against cancer cells but not harmful to healthy cells. This systematic review analyzed flavonoid effectiveness in human cancer chemotherapy. Overall, 22 phase II and 1 phase III clinical trials (PubMed, Scopus, and Web of Science) that used flavonoids as a single agent or combined with other therapeutics against hematopoietic/lymphoid or solid cancer published by January 2019 were selected for analysis. Flavopiridol was the most commonly used flavonoid (at a dose of 50-mg/m2 IV) for all tumor types. Aside from the relatively low rate of complete response (CR) or partial response (PR) with any administration protocol, flavonoids showed higher positive outcomes for hematopoietic and lymphoid tissues (140 patients with CR and 88 with PR among 615 patients in 11 trials) than for solid tumors (4 patients with CR and 21 with PR among 525 patients in 12 trials). However, because of the high variety in administration schedule, more studies are needed to further understand how flavonoids can promote positive outcomes for cancer patients.
Assuntos
Antineoplásicos/administração & dosagem , Flavonoides/administração & dosagem , Neoplasias/tratamento farmacológico , Piperidinas/administração & dosagem , Polifenóis/administração & dosagem , Ensaios Clínicos como Assunto , HumanosRESUMO
OBJECTIVES: An increase in life expectancy is predicted for the general population and, by 2050, about one billion people will be older than 65 years. The Global Cancer Incidence, Mortality and Prevalence database estimates that 1.2 million people of this age will have cancer; this number represents 58% of new cases in the American population. This represents a challenge for diagnosis and treatment, given that some older people have multiple comorbidities and disabilities. MATERIALS AND METHODS: This was a retrospective descriptive study of 204 patients aged 65 years and over. All had a solid tumor that was diagnosed in a private hospital from January 2015 to December 2017. RESULTS: The median age was 72.2 years; the most frequent age group (48.5% of patients) was 65-75 years, and only a small percentage (4.4%) were aged > 85 years. The most common type of cancer was lung cancer (22.5%), followed by colorectal and urinary cancer. Most patients received cancer treatment after the disease diagnosis. CONCLUSION: There are no epidemiological studies of the older oncology population in Mexico. We believe it is necessary to perform larger studies to understand this population and to undertake actions to facilitate greater attention to patient diagnosis, treatment, and alleviation.
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Purpose: The objective of this study was to determine whether a comorbidity index could be used to predict mortality in pediatric patients with chemotherapy-treated solid tumors. Methods: Pediatric patients who underwent chemotherapy treatment for solid tumors were included, and demographic, clinical, and comorbidity data were obtained from patient electronic records. Results: A total of 196 pediatric patients with embryonic solid tumors were included. Metastatic tumors were the most frequently observed (n = 103, 52.6%). The most common comorbidities encountered for the Charlson comorbidity index (CCI) were cellulitis (n = 24, 12.2%) and acute renal failure (n = 15, 7.7%). For the Pediatric Comorbidity Index (PCI), the most frequent comorbidities were pneumonia and sepsis, with n = 64 (32.7%) for each. We evaluated established the prognostic values for both indexes using Kaplan-Meier curves, finding that the CCI and PCI could predict mortality with p < 0.0001. Conclusion: Using the PCI, we observed 100% survival in patients without comorbidities, 70% survival in patients with a low degree of comorbidity, and 20% survival in patients with a high degree of comorbidity. Greater discrimination of probability of survival could be achieved using degrees of comorbidity on the PCI than using degrees of comorbidity on the CCI. The application of the PCI for assessing the hospitalized pediatric population may be of importance for improving clinical evaluation.
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Copaifera multijuga, commonly known as copaiba, is popularly used in the form of tea for various conditions due to the presence of antioxidant substances in its composition, which protect cells against damage caused by free radicals. Its oleoresin is also used as an anti-inflammatory and antitumoral agent. The present study investigated the antioxidant effect of the ethanolic extract of copaiba stem bark on Swiss mice inoculated with solid Ehrlich tumors. Mice were inoculated subcutaneously with 1x106 Ehrlich's tumor cells and treated via gavage with ethanolic extract of copaiba for thirty days, with doses varying between 100 and 200 mg kg-1. Biochemical analyses of enzymatic antioxidants [superoxide dismutase (SOD), catalase (CAT), glutathione-S-transferase (GST)], non-enzymatic antioxidants [reduced glutathione (GSH) and ascorbic acid (ASA)], substances reactive to thiobarbituric acid (TBARS) and protein carbonylation (carbonyl) in different tissues were significantly affected. The extract administered at 200 mg kg-1 presented higher antioxidant capacity in the liver, increased CAT, GST, GSH and decreased TBARS, as well as increased CAT activity and protein carbonylation in brain tissue. The results showed that the copaiba extract was able to reverse the oxidative stress caused by solid Ehrlich tumor, probably due to the presence of antioxidant compounds, and had potential antineoplasic effect after a 30-day treatment. (AU)
Assuntos
Estresse Oxidativo , Radicais Livres , Fabaceae , Neoplasias , AntineoplásicosRESUMO
Copaifera multijuga, commonly known as copaiba, is popularly used in the form of tea for various conditions due to the presence of antioxidant substances in its composition, which protect cells against damage caused by free radicals. Its oleoresin is also used as an anti-inflammatory and antitumoral agent. The present study investigated the antioxidant effect of the ethanolic extract of copaiba stem bark on Swiss mice inoculated with solid Ehrlich tumors. Mice were inoculated subcutaneously with 1x106 Ehrlichs tumor cells and treated via gavage with ethanolic extract of copaiba for thirty days, with doses varying between 100 and 200 mg kg-1. Biochemical analyses of enzymatic antioxidants [superoxide dismutase (SOD), catalase (CAT), glutathione-S-transferase (GST)], non-enzymatic antioxidants [reduced glutathione (GSH) and ascorbic acid (ASA)], substances reactive to thiobarbituric acid (TBARS) and protein carbonylation (carbonyl) in different tissues were significantly affected. The extract administered at 200 mg kg-1 presented higher antioxidant capacity in the liver, increased CAT, GST, GSH and decreased TBARS, as well as increased CAT activity and protein carbonylation in brain tissue. The results showed that the copaiba extract was able to reverse the oxidative stress caused by solid Ehrlich tumor, probably due to the presence of antioxidant compounds, and had potential antineoplasic effect after a 30-day treatment.(AU)
Copaifera multijuga, ou copaíba, é utilizada popularmente como chá para o tratamento de diversas afecções, o que se deve à presença de substâncias antioxidantes em sua composição, que protegem as células contra danos causados pelos radicais livres. O óleo-resina da árvore é usado como antiinflamatório e antitumoral. O presente estudo avaliou o efeito antioxidante do extrato etanólico da casca da copaíba sobre camundongos Swiss machos inoculados com tumor sólido de Ehrlich. Os camundongos foram inoculados subcutaneamente com 1x106 células de tumor de Ehrlich e foram tratados, via gavagem durante 30 dias, com doses de extrato etanólico de copaíba variando de 100 a 200 mg kg-1. Realizou-se análise bioquímica dos antioxidantes enzimáticos [superóxido dismutase (SOD), catalase (CAT), glutationa-S-transferase (GST)], antioxidantes não-enzimáticos [glutationa reduzida (GSH) e ácido ascórbico (ASA)], substâncias reativas ao ácido tiobarbitúrico (TBARS) e carbonilação proteica (carbonil) em diferentes tecidos e apresentando resultados significativos. O extrato administrado na concentração de 200 mg kg-1 apresentou melhor capacidade antioxidante no fígado, aumentando a CAT, GST, GSH e diminuindo TBARS, além de aumentar a atividade da CAT e da carbonilação proteica no tecido cerebral. Os resultados mostram que o extrato de copaíba foi capaz de reverter o estresse oxidativo causado pelo tumor sólido de Ehrlich, provavelmente por conter compostos antioxidantes, e possivelmente teve um efeito antineoplásico após 30 dias de tratamento.(AU)
Assuntos
Animais , Camundongos , Fabaceae/imunologia , Carcinógenos/administração & dosagem , Carcinógenos/farmacologia , Homeopatia , Homeopatia/veterinária , Antioxidantes/administração & dosagem , Antioxidantes/uso terapêutico , Anti-Inflamatórios/imunologia , Anti-Inflamatórios/administração & dosagem , Radicais LivresRESUMO
Current cure rates for retinoblastoma (RB) are very high in developed countries. Nonetheless, in less privileged places worldwide, delayed diagnosis and refusal to adhere to treatment still endure an obstacle to improve overall patient survival. Thus, the access to consistent biomarkers for diagnosis at an earlier stage may facilitate treatment and improve outcomes. Over recent years, much attention has been focused on miRNAs, key post-transcriptional regulators that when altered, largely contribute to carcinogenesis and tumor progression. Many of the ~ 2500 microRNAs described in humans have shown differential expression profiles in tumors. In this review, we summarize current data about the roles of miRNAs in RB along with their value as diagnostic/prognostic factors using electronic databases such as PubMed. We reviewed the importance of miRNA in RB biology and discussed their implications in clinic intervention. Several miRNAs have pointed out reliable diagnostic and prognostic molecular biomarkers. The emergence of targeted therapies has significantly improved cancer treatment. In the near future, the modulation of miRNAs will represent a good treatment strategy.
Assuntos
Perfilação da Expressão Gênica , MicroRNAs/genética , Neoplasias da Retina/genética , Retinoblastoma/genética , Biomarcadores Tumorais , Humanos , MicroRNAs/biossíntese , Prognóstico , Neoplasias da Retina/patologia , Retinoblastoma/patologia , Análise de SobrevidaRESUMO
The present study investigated the antineoplastic effects of pectic polysaccharides that were extracted from green sweet pepper (Capsicum annuum [CAP]) in the Ehrlich carcinoma in mice and in human mammary tumor lineages. After the subcutaneous inoculation of 2 × 106 Ehrlich tumor cells, Female Swiss mice received 50, 100, or 150 mg/kg CAP or vehicle orally once daily or methotrexate (2.5 mg/kg, i.p., every 5 days) for 21 days. CAP dose-dependently reduced Ehrlich tumor growth. It also reduced the viability of MCF-7, MDA-MB-231, and MDA-MB-436 human mammary cell lineages. Treatment with CAP reduced the gene expression of vascular endothelial growth factor in vivo and in vitro, reduced vessel areas of the tumors, and induced necrosis in Ehrlich solid tumors. CAP treatment significantly increased Interleukin-6 in tumors. The antineoplastic effect of CAP appears to depend on the regulation of inflammation and angiogenesis. Further studies are encouraged to better understand the CAP potential for the treatment of breast tumors.
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Antineoplásicos Fitogênicos , Neoplasias da Mama/tratamento farmacológico , Capsicum/química , Carcinoma de Ehrlich/tratamento farmacológico , Neoplasias Mamárias Experimentais/tratamento farmacológico , Pectinas , Animais , Antineoplásicos Fitogênicos/química , Antineoplásicos Fitogênicos/isolamento & purificação , Antineoplásicos Fitogênicos/farmacologia , Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , Carcinoma de Ehrlich/metabolismo , Carcinoma de Ehrlich/patologia , Ensaios de Seleção de Medicamentos Antitumorais , Feminino , Humanos , Células MCF-7 , Neoplasias Mamárias Experimentais/metabolismo , Camundongos , Pectinas/química , Pectinas/isolamento & purificação , Pectinas/farmacologiaRESUMO
Abstract A novel series of platinum (II) complexes was synthesized and the complexes were evaluated for their in vitro cytotoxicity against four human cancer cells lines. Five platinum complexes showed activity against at least one tumor cell line. Complexes 3 and 6 were promising, being active, at micromolar concentrations, against all the assayed tumor cell lines. Compound 3 was selected for further studies in mice with Ehrlich solid tumors and it was able to reduce the rate of tumor growth significantly during the first seven days. However, at the end of the experiments, there was no significant difference between the group of animals treated with 3 and the control group. The low solubility of the compound in the assay conditions can explain, at least in part, these results.
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Animais , Masculino , Feminino , Ratos , Platina/análise , Ensaios de Seleção de Medicamentos Antitumorais/instrumentação , Testes Imunológicos de Citotoxicidade/classificação , Carcinoma de Ehrlich/classificação , Citotoxinas/efeitos adversosRESUMO
Cancer is a complex disease with both genetic and epigenetic origins. The growing field of epigenetics has contributed to our understanding of oncogenesis and tumor progression, and has allowed the development of novel therapeutic drugs. First-generation epigenetic inhibitor drugs have obtained modest clinical results in two types of hematological malignancy. Second-generation epigenetic inhibitors are in development, and have intrinsically greater selectivity for their molecular targets. Solid tumors are more genetic and epigenetically complex than hematological malignancies, but the transcriptome and epigenome biomarkers have been identified for many of these malignancies. This solid tumor molecular aberration profile may be modified using specific or quasi-specific epidrugs together with conventional and innovative anticancer treatments. In this critical review, we briefly analyze the strategies to select the targeted epigenetic changes, enumerate the second-generation epigenetic inhibitors, and describe the main signs indicating the potential of epigenetic therapies in the management of solid tumors. We also highlight the work of consortia or academic organizations that support the undertaking of human epigenetic therapeutic projects as well as some examples of transcriptome/epigenome profile determination in clinical assessment of cancer patients treated with epidrugs. There is a good chance that epigenetic therapies will be able to be used in patients with solid tumors in the future. This may happen soon through collaboration of diverse scientific groups, making the selection of targeted epigenetic aberration(s) more rapid, the design and probe of drug candidates, accelerating in vitro and in vivo assays, and undertaking new cancer epigenetic-therapy clinical trails.
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The aim of this study was to investigate the effect of the mushroom Agaricus blazeii Murril (ABM) extracts on the hematological profile of Swiss mice bearing an Ehrlich solid tumor. Three fractions (total extract, polysaccharides, and supernatant) of ABM extracts obtained by four methods (ultrasonic or water bath, at pH 4 or pH 7) were administered to mice over 21 days. Polysaccharide solutions were analyzed by gas and liquid chromatography that showed both mannose and glucose concentrations. The method of extraction influenced the degree of glucose polymerization and the mannose/glucose relationship. The treatment with ABM supernatant at pH 7 and water bath was associated with reduced concentrations of leukocytes and lymphocytes and altered the percentage of CD4+ and CD8+ lymphocytes in Ehrlich tumor-bearing mice. The treatment with the ABM extract in water bath and ultrasound at pH 4 resulted in lower lymphocyte counts, regardless of tumor presence, and greater granulocyte values in mice with Ehrlich tumor than in controls. We concluded that different fractions and methods of extraction of A. blazei produced differing blood profiles in mice inoculated with the Ehrlich tumor.
O objetivo deste estudo foi investigar o efeito de diferentes extratos do cogumelo Agaricus blazeii Murril (ABM) sobre o perfil hematológico de camundongos Swiss portadores de tumor de Ehrlich sólido. Três frações (extrato total, polissacarídeos e sobrenadante) dos extratos de ABM foram obtidas por quatro métodos (sonificador, banho-maria, em pH 4 ou pH 7) e administradas para camundongos durante 21 dias. Soluções de polissacarídeos foram analisadas por cromatografia gasosa e líquida, que mostraram concentrações de glucose e manose. O método de extração influenciou o grau de polimerização da glicose e a relação manose/glucose. O tratamento com o sobrenadante de ABM (em pH 7 e banho-maria) estava associado com reduzidas concentrações de leucócitos e linfócitos, além de alterar a porcentagem de linfócitos CD4+ e CD8+ em camundongos portadores de tumor sólido de Ehrlich. O tratamento com extratos de ABM, obtidos tanto em banho-maria como no sonificador em pH 4, resultou nas mais baixas contagens de linfócitos, independentemente da presença do tumor, e nos maiores valores de granulócitos em camundongos com tumor de Ehrlich. Conclui-se que os diferentes métodos de extração com as respectivas frações de A. blazei são capazes de intereferir no perfil hematológico de camundongos com tumor sólido de Ehrlich.
Assuntos
Animais , Feminino , Camundongos , Agaricus , Carcinoma de Ehrlich/terapia , Extratos Vegetais/uso terapêutico , Glucose/química , Manose/química , Métodos Analíticos de Preparação de Amostras/veterinária , Polimerização , Polissacarídeos/administração & dosagem , Testes Sorológicos/veterináriaRESUMO
The aim of this study was to investigate the effect of the mushroom Agaricus blazeii Murril (ABM) extracts on the hematological profile of Swiss mice bearing an Ehrlich solid tumor. Three fractions (total extract, polysaccharides, and supernatant) of ABM extracts obtained by four methods (ultrasonic or water bath, at pH 4 or pH 7) were administered to mice over 21 days. Polysaccharide solutions were analyzed by gas and liquid chromatography that showed both mannose and glucose concentrations. The method of extraction influenced the degree of glucose polymerization and the mannose/glucose relationship. The treatment with ABM supernatant at pH 7 and water bath was associated with reduced concentrations of leukocytes and lymphocytes and altered the percentage of CD4+ and CD8+ lymphocytes in Ehrlich tumor-bearing mice. The treatment with the ABM extract in water bath and ultrasound at pH 4 resulted in lower lymphocyte counts, regardless of tumor presence, and greater granulocyte values in mice with Ehrlich tumor than in controls. We concluded that different fractions and methods of extraction of A. blazei produced differing blood profiles in mice inoculated with the Ehrlich tumor(AU)
O objetivo deste estudo foi investigar o efeito de diferentes extratos do cogumelo Agaricus blazeii Murril (ABM) sobre o perfil hematológico de camundongos Swiss portadores de tumor de Ehrlich sólido. Três frações (extrato total, polissacarídeos e sobrenadante) dos extratos de ABM foram obtidas por quatro métodos (sonificador, banho-maria, em pH 4 ou pH 7) e administradas para camundongos durante 21 dias. Soluções de polissacarídeos foram analisadas por cromatografia gasosa e líquida, que mostraram concentrações de glucose e manose. O método de extração influenciou o grau de polimerização da glicose e a relação manose/glucose. O tratamento com o sobrenadante de ABM (em pH 7 e banho-maria) estava associado com reduzidas concentrações de leucócitos e linfócitos, além de alterar a porcentagem de linfócitos CD4+ e CD8+ em camundongos portadores de tumor sólido de Ehrlich. O tratamento com extratos de ABM, obtidos tanto em banho-maria como no sonificador em pH 4, resultou nas mais baixas contagens de linfócitos, independentemente da presença do tumor, e nos maiores valores de granulócitos em camundongos com tumor de Ehrlich. Conclui-se que os diferentes métodos de extração com as respectivas frações de A. blazei são capazes de intereferir no perfil hematológico de camundongos com tumor sólido de Ehrlich(AU)
Assuntos
Animais , Feminino , Camundongos , Agaricus , Carcinoma de Ehrlich/terapia , Testes Sorológicos/veterinária , Polissacarídeos/administração & dosagem , Polimerização , Glucose/química , Manose/química , Métodos Analíticos de Preparação de Amostras/veterinária , Extratos Vegetais/uso terapêuticoRESUMO
Se presenta el caso de una paciente de 21 años de edad, portadora de un tumor sólido quístico pseudopapilar del páncreas. Se hace una revisión de los aspectos clínicos, diagnósticos y terapéuticos de esta rara neoplasia; al mismo tiempo, se hace énfasis en la anatomía patológica y en su diagnóstico diferencial. Esta es una entidad propia de mujeres jóvenes, sin embargo, en la actualidad ha incrementado su frecuencia, con variación en los aspectos clásicos del comportamiento clínico.
The case of a 21-year female patient with a solid-pseudopapillary tumor of the Pancreas is presented. Clinical, histopathological, diagnostic and therapeutic features of this rare tumor are presented and discussed with emphasis on pathology and differential diagnosis. This rare entity most frequently affects young women, but its incidence has increasing, and there have been changes its clinical behavior from those classically reported.