RESUMEN
Although osteosarcoma is a rare disease, with a global incidence rate estimated at 5.0/million/year, it is the most frequent primary bone sarcoma in children and adolescents. In translational research, the patient-derived xenograft (PDX) model is considered an authentic in vivo model for several types of cancer, as tumorgrafts faithfully retain the biological characteristics of the primary tumors. Our goal was to investigate the association between PDX formation and clinical findings of osteosarcoma patients and the ability of the model to preserve in immunocompromized mice the characteristics of the parental tumor. A fresh sample of the patient tumor obtained from a representative biopsy or from surgical resection was implanted into nude mice. When tumor outgrowths reached ~1,500mm³, fresh PDX fragments were re-transplanted into new hosts. Engraftment in mice was obtained after a latency period of 19-225 days (median 92 days) in 40.54% of the implanted samples. We confirmed the histopathological fidelity between the patient tumor and their respective established PDXs, including the expression of biomarkers. PDX take rate was higher in surgical resection samples, in post-chemotherapy surgical samples and in samples from patients with metastatic disease at presentation. In conclusion, we have shown that the osteosarcoma PDX model reliably recapitulates the morphological aspects of the human disease after serial passage in mice. The observation that more aggressive forms of osteosarcoma, including those with metastatic disease at presentation, have a higher efficiency to generate PDXs provides a promising scenario to address several unanswered issues in clinical oncology.
Asunto(s)
Neoplasias Óseas/patología , Proliferación Celular , Osteosarcoma/secundario , Adolescente , Adulto , Animales , Biomarcadores de Tumor/metabolismo , Neoplasias Óseas/metabolismo , Neoplasias Óseas/cirugía , Niño , Femenino , Humanos , Masculino , Ratones Desnudos , Persona de Mediana Edad , Trasplante de Neoplasias , Osteosarcoma/metabolismo , Osteosarcoma/cirugía , Fenotipo , Factores de Tiempo , Trasplante Heterólogo , Carga Tumoral , Adulto JovenRESUMEN
Abstract INTRODUCTION Ectopic forms of schistosomiasis are those in which the parasitic element is localized outside the portal system, the natural habitat of the helminth. Although the prevalence rates of schistosomiasis are high in Brazil, clinical and epidemiological data on ectopic forms of the disease are still scarce. METHODS Cross-sectional, retrospective and descriptive epidemiological study in which cases with a confirmed histopathological diagnosis of an ectopic form of schistosomiasis were analyzed. The cases were selected from a database of the anatomic pathology files of a referral center. RESULTS Of the 21 cases identified, seven affected the female genital tract and five the male genital tract; four cases were identified in the peritoneum; two cases involved lymph nodes and two involved adipose tissue; and renal involvement was detected in one case. CONCLUSIONS The lack of knowledge of the clinical presentation of ectopic forms of schistosomiasis makes the early identification and treatment of this form difficult, with direct implications in the reduction of morbidity and mortality in endemic areas.
Asunto(s)
Humanos , Masculino , Femenino , Adulto , Anciano , Anciano de 80 o más Años , Adulto Joven , Esquistosomiasis mansoni/epidemiología , Esquistosomiasis mansoni/diagnóstico , Esquistosomiasis mansoni/patología , Brasil/epidemiología , Prevalencia , Estudios Transversales , Estudios Retrospectivos , Persona de Mediana EdadRESUMEN
INTRODUCTION: Ectopic forms of schistosomiasis are those in which the parasitic element is localized outside the portal system, the natural habitat of the helminth. Although the prevalence rates of schistosomiasis are high in Brazil, clinical and epidemiological data on ectopic forms of the disease are still scarce. METHODS: Cross-sectional, retrospective and descriptive epidemiological study in which cases with a confirmed histopathological diagnosis of an ectopic form of schistosomiasis were analyzed. The cases were selected from a database of the anatomic pathology files of a referral center. RESULTS: Of the 21 cases identified, seven affected the female genital tract and five the male genital tract; four cases were identified in the peritoneum; two cases involved lymph nodes and two involved adipose tissue; and renal involvement was detected in one case. CONCLUSIONS: The lack of knowledge of the clinical presentation of ectopic forms of schistosomiasis makes the early identification and treatment of this form difficult, with direct implications in the reduction of morbidity and mortality in endemic areas.
Asunto(s)
Esquistosomiasis mansoni/epidemiología , Adulto , Anciano , Anciano de 80 o más Años , Brasil/epidemiología , Estudios Transversales , Femenino , Humanos , Masculino , Persona de Mediana Edad , Prevalencia , Estudios Retrospectivos , Esquistosomiasis mansoni/diagnóstico , Esquistosomiasis mansoni/patología , Adulto JovenRESUMEN
The pathogenic role of inflammation and oxidative stress in chronic kidney disease (CKD) is well known. Anti-inflammatories and antioxidant drugs has demonstrated significant renoprotection in experimental nephropathies. Moreover, the inclusion of natural antioxidants derived from food and herbal extracts (such as polyphenols, curcumin and lycopene) as an adjuvant therapy for slowing CKD progression has been largely tested. Brazilian propolis is a honeybee product, whose anti-inflammatory, antimicrobial and antioxidant effects have been widely shown in models of sepsis, cancer, skin irritation and liver fibrosis. Furthermore, previous studies demonstrated that this compound promotes vasodilation and reduces hypertension. However, potential renoprotective effects of propolis in CKD have never been investigated. The aim of this study was to evaluate the effects of a subtype of Brazilian propolis, the Red Propolis (RP), in the 5/6 renal ablation model (Nx). Adult male Wistar rats underwent Nx and were divided into untreated (Nx) and RP-treated (Nx+RP) groups, after 30 days of surgery; when rats already exhibited marked hypertension and proteinuria. Animals were observed for 90 days from the surgery day, when Nx+RP group showed significant reduction of hypertension, proteinuria, serum creatinine retention, glomerulosclerosis, renal macrophage infiltration and oxidative stress, compared to age-matched untreated Nx rats, which worsened progressively over time. In conclusion, RP treatment attenuated hypertension and structural renal damage in Nx model. Reduction of renal inflammation and oxidative stress could be a plausible mechanism to explain this renoprotection.
Asunto(s)
Antiinflamatorios/administración & dosificación , Antioxidantes/administración & dosificación , Hipertensión Renal/tratamiento farmacológico , Própolis/administración & dosificación , Proteinuria/tratamiento farmacológico , Animales , Antiinflamatorios/uso terapéutico , Antioxidantes/uso terapéutico , Creatinina/sangre , Modelos Animales de Enfermedad , Hipertensión Renal/etiología , Riñón/efectos de los fármacos , Riñón/patología , Masculino , Nefrectomía , Própolis/uso terapéutico , Proteinuria/etiología , Ratas , Ratas Wistar , Insuficiencia Renal Crónica/prevención & controlRESUMEN
OBJECTIVES: to evaluate the antimicrobial, cytotoxic and healing activities of the ethanolic extract of the stems of Z. tuberculosa via topical use and/or oral ingestion. METHOD: antimicrobial assays in vitro using the disk diffusion method, the Artemia salina toxicity test, and in vivo assays with Wistar rats. From these was collected clinical, histological and biochemical data for evaluating the healing process. RESULTS: in vitro antimicrobial testing showed activity in relation to Streptococcus pyogenes, Staphylococcus aureus and Staphylococcus epidermidis, with zones of inhibition of 18, 14 and 10 mm, respectively. The best minimum inhibitory concentration was 62.5 µg/ml for S. aureus, this bacteria being chosen for the in vitro assays. Animals treated with the ointments with the extract of Z. tuberculosa showed the best results in the reduction of the wound diameter, data confirmed by the presence of re-epithelialization in the histological samples. CONCLUSION: the extract was shown to be promising for the continuation of studies which may identify the active ingredients responsible for the pharmacological activity and its mechanism of action in the process of wound healing, so as to develop a product which may be used as an alternate means in the repair of infected cutaneous wounds.
Asunto(s)
Bignoniaceae , Fitoterapia , Extractos Vegetales/farmacología , Cicatrización de Heridas/efectos de los fármacos , Animales , Pruebas de Sensibilidad Microbiana , Ratas , Ratas WistarRESUMEN
OBJETIVO: Avaliar a ação cicatrizante de própolis verde e vermelha, correlacionando ao teor de flavonoides MÉTODOS: Foi realizada a quantificação de flavonoides totais dos extratos etanólicos de própolis verde e vermelha para posterior incorporação em pomada base a 20%. Utilizou-se 20 ratos Wistar distribuídos em quatro grupos: solução salina a 0,9% (S), pomada base (B), pomada própolis verde (G), pomada própolis vermelha (R), todos submetidos à confecção de lesões excisivas na região mediana do dorso. Os ratos foram tratados diariamente durante 15 dias. Neste período foram observados peso; temperatura corporal; diâmetro das feridas. Para análise histológica, amostras das feridas foram coletadas. Ao fim do experimento foram realizadas coleta sanguínea e remoção do rim e fígado para análises bioquímica e histológica. RESULTADOS: Os teores de flavonoides totais das própolis verde (4,50 %) e vermelha (5,92 %) foram elevados (>2 %), mas, embora a segunda apresente teor maior que a primeira, a evolução da própolis verde, macro e histologicamente, foi melhor na reparação das feridas. Não foram observadas nefro ou hepatotoxicidade, resultado corroborado pelos ensaios bioquímicos (TGP e albumina). A própolis influiu na redução de colesterol total, triglicerídeos e glicemia. CONCLUSÃO: Não foi possível correlacionar o teor de flavonoides totais com a ação cicatrizante da própolis. O dado revela a necessidade da elucidação dos flavonoides encontrados em cada classe de própolis para desvendar qual (ou quais) flavonoide(s) seria(m) representativo(s) no processo cicatricial.
OBJECTIVE: To evaluate the healing action of green and red propolis, correlating it with the content of flavonoids. METHODS: We performed quantification of total flavonoids of green and red propolis ethanol extracts for subsequent incorporation in ointment base to 20%. We used 20 Wistar rats divided into four groups: 0.9% saline (S), ointment base (B), green propolis ointment (G) and red propolis ointment (R). All animals were submitted to excisional lesions in the midian back region. The rats were treated daily for 15 days. During this period we observed weight, body temperature and diameters of the wounds. For histological analysis, samples were collected from wounds. At the end of the experiment we performed blood collection and removal of the kidney and liver for biochemical and histological analyzes. RESULTS: The levels of total flavonoids of green (4.50%) and red (5.92%) propolis were high (> 2%), but, while the latter showed a content larger than the former, the evolution of green propolis was better in the repair of wounds, both macroscopically and histologically. There were no nephrotoxicity or hepatotoxicity, a result confirmed by biochemical tests (ALT and albumin). Propolis influenced the reduction of total cholesterol, triglycerides and glucose. CONCLUSION: There was no correlation between total flavonoid contents and the healing action of propolis. This reveals the need for elucidation of the flavonoids found in each class of propolis to unravel which one(s) would be important for the healing process.
Asunto(s)
Animales , Masculino , Ratas , Própolis/uso terapéutico , Cicatrización de Heridas/efectos de los fármacos , Flavonoides/análisis , Própolis/química , Ratas WistarRESUMEN
OBJECTIVE: To evaluate the healing action of green and red propolis, correlating it with the content of flavonoids. METHODS: We performed quantification of total flavonoids of green and red propolis ethanol extracts for subsequent incorporation in ointment base to 20%. We used 20 Wistar rats divided into four groups: 0.9% saline (S), ointment base (B), green propolis ointment (G) and red propolis ointment (R). All animals were submitted to excisional lesions in the midian back region. The rats were treated daily for 15 days. During this period we observed weight, body temperature and diameters of the wounds. For histological analysis, samples were collected from wounds. At the end of the experiment we performed blood collection and removal of the kidney and liver for biochemical and histological analyzes. RESULTS: The levels of total flavonoids of green (4.50%) and red (5.92%) propolis were high (> 2%), but, while the latter showed a content larger than the former, the evolution of green propolis was better in the repair of wounds, both macroscopically and histologically. There were no nephrotoxicity or hepatotoxicity, a result confirmed by biochemical tests (ALT and albumin). Propolis influenced the reduction of total cholesterol, triglycerides and glucose. CONCLUSION: There was no correlation between total flavonoid contents and the healing action of propolis. This reveals the need for elucidation of the flavonoids found in each class of propolis to unravel which one(s) would be important for the healing process.
Asunto(s)
Própolis/uso terapéutico , Cicatrización de Heridas/efectos de los fármacos , Animales , Flavonoides/análisis , Masculino , Própolis/química , Ratas , Ratas WistarRESUMEN
Atypical glandular cells are a common finding in cervical cytology in cervical cancer screening and its occurrence has increased in the last decades. The identification of these cells is clinically very important due to its association with cervical and endometrial dysplasic lesions and cancer. Using a systematic approach, this article reviewed studies investigating cervical lesions that are characteristic in patients previously diagnosed as having atypical glandular cells. Studies in which diagnostic investigation did not include histopathological diagnosis were excluded. A comprehensive search for available material in LILACS, SciELO, PubMed/ Medline and Old Medline databases, dated between 1966 and 2009 was performed. Articles omitted by the electronic database search were also included. Nineteen articles met the inclusion criteria and were selected. This report aims at evaluating whether atypical glandular cells, initially found in cervical cytology and subsequently identified at the histological analysis, are related to the presence of benign, pre-malignant and malignant lesions. Eleven out of 19 selected articles showed the highest correlation between atypical glandular cells with benign diseases and six with squamous pre-malignant lesions.
Asunto(s)
Adenocarcinoma/patología , Cuello del Útero/patología , Neoplasias del Cuello Uterino/patología , Adenocarcinoma/diagnóstico , Femenino , Humanos , Neoplasias del Cuello Uterino/diagnóstico , Frotis Vaginal , Displasia del Cuello del Útero/diagnóstico , Displasia del Cuello del Útero/patologíaRESUMEN
Atipias de células glandulares em esfregaços cervicovaginais é um achado citológico na rotina de rastreamento do câncer cervical, que aumentou nas últimas décadas. Sua constatação é importante clinicamente, pois é alta a percentagem de casos associados com doença cervical e endometrial de alto grau e câncer. Este trabalho avaliou, por meio de uma revisão sistemática, estudos que investigaram o perfil das lesões de colo uterino em avaliações histológicas de seguimento de pacientes já diagnosticadas com células glandulares atípicas. Foram excluídos os estudos cuja investigação diagnóstica não incluísse o diagnóstico histopatológico. Realizou-se uma busca abrangente de publicações no período de 1966 a 2009, nas bases do LILACS, SciELO, PubMed/Medline e Old Medline. Os artigos omitidos na busca eletrônica também foram incluídos. Estavam de acordo com os critérios de inclusão 19 artigos, que foram selecionados. Este estudo tem como objetivo avaliar se a atipia celular glandular observada inicialmente na citologia relacionava-se histologicamente com a presença de lesões benignas, pré-neoplásicas ou neoplásicas. Dos 19 estudos selecionados, 11 mostraram maior correlação entre atipia glandular com patologias benignas e seis com lesões escamosas pré-malignas.
Atypical glandular cells are a common finding in cervical cytology in cervical cancer screening and its occurrence has increased in the last decades. The identification of these cells is clinically very important due to its association with cervical and endometrial dysplasic lesions and cancer. Using a systematic approach, this article reviewed studies investigating cervical lesions that are characteristic in patients previously diagnosed as having atypical glandular cells. Studies in which diagnostic investigation did not include histopathological diagnosis were excluded. A comprehensive search for available material in LILACS, SciELO, PubMed/ Medline and Old Medline databases, dated between 1966 and 2009 was performed. Articles omitted by the electronic database search were also included. Nineteen articles met the inclusion criteria and were selected. This report aims at evaluating whether atypical glandular cells, initially found in cervical cytology and subsequently identified at the histological analysis, are related to the presence of benign, pre-malignant and malignant lesions. Eleven out of 19 selected articles showed the highest correlation between atypical glandular cells with benign diseases and six with squamous pre-malignant lesions.