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1.
Am J Clin Oncol ; 42(2): 221-227, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30540568

RESUMO

BACKGROUND: Complete tumor removal by transsphenoidal surgery is usually difficult for large nonfunctioning pituitary adenomas (NFPAs). A validated medical treatment may be useful for their management. This study evaluates the clinical efficacy of the dopaminergic agonist cabergoline for residual NFPA. DESIGN, SETTING, AND PARTICIPANTS: We conducted a randomized, parallel, open-label clinical trial that compared cabergoline with nonintervention in patients with residual NFPA after transsphenoidal surgery over 2 years. The primary outcome was clinical efficacy (tumor reduction). The secondary outcome was the relationship between tumor dopamine D2 receptor (D2R) expression and clinical responsiveness. Tumor measurements and clinical evaluations were performed every 6 months. RESULTS: In total, 59 and 57 individuals were randomly assigned to the study and control groups, respectively. At the end of the study, residual tumor shrinkage, stabilization, and enlargement were observed in 28.8%, 66.1%, and 5.1% of patients, respectively, in the medical-therapy group and in 10.5%, 73.7%, and 15.8% of patients, respectively, in the control group (P=0.01). The progression-free survival rate was 23.2 and 20.8 months for the study and control groups, respectively (P=0.01). D2R was not associated with cabergoline responsiveness. No major side effects were related to cabergoline use. CONCLUSIONS: Cabergoline was an effective drug for treating residual NFPA, and its use was associated with a high rate of tumor shrinkage (ClinicalTrials.gov NCT03271918).


Assuntos
Adenoma/tratamento farmacológico , Antiparkinsonianos/uso terapêutico , Cabergolina/uso terapêutico , Neoplasia Residual/tratamento farmacológico , Neoplasias Hipofisárias/tratamento farmacológico , Adenoma/metabolismo , Adenoma/patologia , Gerenciamento Clínico , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasia Residual/metabolismo , Neoplasia Residual/patologia , Neoplasias Hipofisárias/metabolismo , Neoplasias Hipofisárias/patologia , Prognóstico , Receptores de Dopamina D2/metabolismo , Taxa de Sobrevida
2.
Oncotarget ; 9(18): 14160-14174, 2018 Mar 06.
Artigo em Inglês | MEDLINE | ID: mdl-29581835

RESUMO

Oxysterols are cholesterol oxygenated derivatives which possess several biological actions. Among oxysterols, 7-ketocholesterol (7KC) is known to induce cell death. Here, we hypothesized that 7KC cytotoxicity could be applied in cancer therapeutics. 7KC was incorporated into a lipid core nanoemulsion. As a cellular model the murine melanoma cell line B16F10 was used. The nanoparticle (7KCLDE) uptake into tumor cells was displaced by increasing amounts of low-density-lipoproteins (LDL) suggesting a LDL-receptor-mediated cell internalization. 7KCLDE was mainly cytostatic, which led to an accumulation of polyploid cells. Nevertheless, a single dose of 7KCLDE killed roughly 10% of melanoma cells. In addition, it was observed dissipation of the transmembrane potential, evidenced with flow cytometry; presence of autophagic vacuoles, visualized and quantified with flow cytometry and acridine orange; and presence of myelin figures, observed with ultrastructural microscopy. 7KCLDE impaired cytokenesis was accompanied by changes in cellular morphology into a fibroblastoid shape which is supported by cytoskeletal rearrangements, as shown by the increased actin polymerization. 7KCLDE was injected into B16 melanoma tumor-bearing mice. 7KCLDE accumulated in the liver and tumor. In melanoma tumor 7KCLDE promoted a >50% size reduction, enlarged the necrotic area, and reduced intratumoral vasculature. 7KCLDE increased the survival rates of animals, without hematologic or liver toxicity. Although more pre-clinical studies should be performed, our preliminary results suggested that 7KCLDE is a promising novel preparation for cancer chemotherapy.

3.
Oncotarget, v. 9, n. 18, p. 14160-14174, 2018
Artigo em Inglês | Sec. Est. Saúde SP, SESSP-IBPROD, Sec. Est. Saúde SP | ID: bud-2519

RESUMO

Oxysterols are cholesterol oxygenated derivatives which possess several biological actions. Among oxysterols, 7-ketocholesterol (7KC) is known to induce cell death. Here, we hypothesized that 7KC cytotoxicity could be applied in cancer therapeutics. 7KC was incorporated into a lipid core nanoemulsion. As a cellular model the murine melanoma cell line B16F10 was used. The nanoparticle (7KCLDE) uptake into tumor cells was displaced by increasing amounts of low-density-lipoproteins (LDL) suggesting a LDL-receptor-mediated cell internalization. 7KCLDE was mainly cytostatic, which led to an accumulation of polyploid cells. Nevertheless, a single dose of 7KCLDE killed roughly 10% of melanoma cells. In addition, it was observed dissipation of the transmembrane potential, evidenced with flow cytometry; presence of autophagic vacuoles, visualized and quantified with flow cytometry and acridine orange; and presence of myelin figures, observed with ultrastructural microscopy. 7KCLDE impaired cytokenesis was accompanied by changes in cellular morphology into a fibroblastoid shape which is supported by cytoskeletal rearrangements, as shown by the increased actin polymerization. 7KCLDE was injected into B16 melanoma tumor-bearing mice. 7KCLDE accumulated in the liver and tumor. In melanoma tumor 7KCLDE promoted a > 50% size reduction, enlarged the necrotic area, and reduced intratumoral vasculature. 7KCLDE increased the survival rates of animals, without hematologic or liver toxicity. Although more pre-clinical studies should be performed, our preliminary results suggested that 7KCLDE is a promising novel preparation for cancer chemotherapy.

4.
Oncotarget ; 9(18): p. 14160-14174, 2018.
Artigo em Inglês | Sec. Est. Saúde SP, SESSP-IBPROD, Sec. Est. Saúde SP | ID: but-ib15289

RESUMO

Oxysterols are cholesterol oxygenated derivatives which possess several biological actions. Among oxysterols, 7-ketocholesterol (7KC) is known to induce cell death. Here, we hypothesized that 7KC cytotoxicity could be applied in cancer therapeutics. 7KC was incorporated into a lipid core nanoemulsion. As a cellular model the murine melanoma cell line B16F10 was used. The nanoparticle (7KCLDE) uptake into tumor cells was displaced by increasing amounts of low-density-lipoproteins (LDL) suggesting a LDL-receptor-mediated cell internalization. 7KCLDE was mainly cytostatic, which led to an accumulation of polyploid cells. Nevertheless, a single dose of 7KCLDE killed roughly 10% of melanoma cells. In addition, it was observed dissipation of the transmembrane potential, evidenced with flow cytometry; presence of autophagic vacuoles, visualized and quantified with flow cytometry and acridine orange; and presence of myelin figures, observed with ultrastructural microscopy. 7KCLDE impaired cytokenesis was accompanied by changes in cellular morphology into a fibroblastoid shape which is supported by cytoskeletal rearrangements, as shown by the increased actin polymerization. 7KCLDE was injected into B16 melanoma tumor-bearing mice. 7KCLDE accumulated in the liver and tumor. In melanoma tumor 7KCLDE promoted a > 50% size reduction, enlarged the necrotic area, and reduced intratumoral vasculature. 7KCLDE increased the survival rates of animals, without hematologic or liver toxicity. Although more pre-clinical studies should be performed, our preliminary results suggested that 7KCLDE is a promising novel preparation for cancer chemotherapy.

5.
J. bras. patol. med. lab ; 52(6): 416-425, Nov.-Dec. 2016. tab, graf
Artigo em Inglês | LILACS, Sec. Est. Saúde SP, SESSP-CTDPROD, Sec. Est. Saúde SP, SESSP-IALPROD, Sec. Est. Saúde SP, SESSP-IALACERVO | ID: biblio-841215

RESUMO

ABSTRACT Introduction: Epstein-Barr virus (EBV) may serve as a target in therapeutic treatments, thus reliable diagnostic results are necessary. Objective: The aim of this study was to evaluate the accuracy of EBV detection by in situ hybridization (ISH) using five commercial probes in formalin-fixed and paraffin-embedded samples of nodular sclerosis Hodgkin's lymphoma (HL), and to compare the results with immunohistochemistry (IHC) and polymerase chain reaction (PCR). Material and method: Thirty samples were selected, 28 were lymph nodes, one bone marrow and one mediastinum. The following parameters were analyzed: signal intensity; proportionality of positive cells; quality of the reaction according to comfort for evaluation, sign quality and homogeneity of labeled cells; background reaction; morphology; presence of artifacts; and positivity in other non-neoplastic cells. All samples were analyzed for EBV detection using the five probes, IHC for latent membrane protein type 1 (LMP1) and PCR for Epstein Barr virus nuclear antigen 1 (EBNA1). Statistical analyses were performed with the R1 software; Fleiss' test and Cohen Kappa index of 5% were considered significant. Results: The detection by IHC-LMP1 was 26.7% (8/30) and 66.7% (20/30) by PCR-EBNA1. All probes detected EBV. Positivity was observed in 42/90 (46.7%), 38/90 (42.2%), 45/90 (50%), 27/90 (30%) and 61/90 (67.8%) for probes A, B, C, D and E, respectively. Discussion: All five probes demonstrated positivity. Conclusion: Probe E showed better rate (67.8%), sensitivity, specificity and accuracy (100%), a very good correlation among the different observers and with PCR, besides great cost-benefits relation.


RESUMO Introdução: O vírus Epstein-Barr (EBV) pode servir como alvo nos tratamentos terapêuticos, sendo necessário resultado diagnóstico confiável. Objetivo: Avaliar a acurácia da detecção do EBV pela hibridização in situ (ISH), utilizando cinco sondas comerciais em amostras fixadas em formalina e incluídas em parafina de linfoma de Hodgkin (LH) esclerose nodular, comparando os resultados com a imuno-histoquímica (IHQ) e a reação em cadeia pela polimerase (PCR). Material e método: Trinta amostras foram selecionadas, sendo 28 linfonodos, uma medula óssea e um mediastino. Os seguintes parâmetros foram analisados: intensidade do sinal; proporcionalidade das células positivas; qualidade da reação de acordo com o conforto na avaliação, qualidade do sinal e homogeneidade das células marcadas; reação de fundo; morfologia; presença de artefatos; e positividade em outras células não neoplásicas. Todas as amostras foram analisadas para a detecção do EBV usando as cinco sondas, IHQ para proteína da membrana latente tipo 1 (LMP1) e PCR para antígeno nuclear do EBV (EBNA1). As análises estatísticas foram realizadas com o software R1; os índices de 5% para Kappa de Fleiss e Cohen foram considerados significantes. Resultados: A detecção pela IHQ-LMP1 foi de 26,7% (8/30) e 66,7% (20/30) pela PCR-EBNA1. Todas as sondas detectaram EBV. A positividade foi observada em 42/90 (46,7%), 38/90 (42,2%), 45/90 (50%), 27/90 (30%) e 61/90 (67,8%) para as sondas A, B, C, D e E, respectivamente. Discussão: Todas as sondas demonstraram positividade. Conclusão: A sonda E mostrou melhor taxa (67,8%), sensibilidade, especificidade e precisão (100%), boa correlação entre os diferentes observadores e com a PCR, além de ótimo custo/benefício.


Assuntos
Vírus
6.
BMC Neurol ; 15: 159, 2015 Sep 02.
Artigo em Inglês | MEDLINE | ID: mdl-26329680

RESUMO

BACKGROUND: Association of leukoencephalopathy and atypical mycobacteriosis has been rarely reported. We present a case that is relevant for its unusual presentation and because it may shed further light on the pathogenic mechanisms underlying reversible encephalopathies. CASE REPORT: We report the case of a Hispanic 64-year-old woman with cognitive decline and extensive leukoencephalopathy. Magnetic resonance imaging revealed white-matter lesions with increased water diffusivity, without blood-brain-barrier disruption. Brain biopsy showed tissue rarefaction with vacuolation, mild inflammation, few reactive astrocytes and decreased aquaporin water-channel expression in the lesions. Six months later, she was diagnosed with atypical mycobacterial pulmonary infection. Brain lesions resolved after antimycobacterial treatment. CONCLUSION: We hypothesize leukoencephalopathic changes and vasogenic edema were associated with decreased aquaporin expression. Further studies should clarify if reversible leukoencephalopathy has a causal relationship with decreased aquaporin expression and atypical mycobacterial infection, and mechanisms underlying leukoencephalopathy resolution after antimycobacterial treatment. This article may contribute to the understanding of pathogenic mechanisms underlying magnetic resonance imaging subcortical lesions and edema, which remain incompletely understood.


Assuntos
Leucoencefalopatias/tratamento farmacológico , Pneumopatias/tratamento farmacológico , Infecções por Mycobacterium não Tuberculosas/tratamento farmacológico , Antibacterianos/uso terapêutico , Transtornos Cognitivos/tratamento farmacológico , Transtornos Cognitivos/etiologia , Feminino , Humanos , Leucoencefalopatias/etiologia , Leucoencefalopatias/patologia , Pneumopatias/diagnóstico , Pneumopatias/microbiologia , Imageamento por Ressonância Magnética , Pessoa de Meia-Idade , Infecções por Mycobacterium não Tuberculosas/diagnóstico , Micobactérias não Tuberculosas , Substância Branca/patologia
7.
Int J Surg Case Rep ; 7C: 168-71, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-25648470

RESUMO

INTRODUCTION: Chordoid glioma is a rare low-grade brain tumor originating from the anterior wall of the third ventricle. CASE PRESENTATION: A 13-year-old female with progressive intermittent holocranial headaches and a diagnosis of chordoid glioma underwent tumor resection in our neuro-oncology unit. DISCUSSION: We review all 79 cases of chordoid glioma reported in the literature so far, focusing on the diagnostic criteria, treatment options and prognosis. CONCLUSION: Efficient treatment of chordoid glioma depends upon radical surgical resection. Based on the reviewed data, which showed high morbi-mortality rates for this kind of tumor, we recommend a more conservative treatment approach.

8.
J Histochem Cytochem ; 55(10): 1015-26, 2007 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-17565118

RESUMO

Beta1-6 branching of N-linked oligosaccharides has been correlated with the progression of different cancers. The leukoagglutinins of Phaseolus vulgaris (L-PHA) have been used to study this pattern of glycosylation whose biological significance is incompletely understood. The animal lectin, galectin-3, also binds to structures recognized by L-PHA. To develop a functional tool for the in situ identification of this pattern of glycosylation, human galectin-3 was fused to bacterial alkaline phosphatase (gal3/AP). Gal3/AP recognized both A and B blood group saccharides (B>A) and lactosamine derivatives. Gal3/AP recognition depended at least in part on the N-linked oligosaccharides of different glycoproteins. The presence and distribution of galectin-3 ligands were analyzed in both murine and human normal and tumor samples. Loss of apical expression of galectin-3 ligands was commonly found in carcinomas. Endothelial and inflammatory cells were enriched in galectin-3 ligands as compared with tumor cells; thus, gal3/AP is a suitable tool for studying tumor microenvironments. Comparative analysis of both gal3/AP and L-PHA binding patterns indicated that although similar, these patterns are not identical. The probe developed was useful for several immunoenzymatic assays and will allow the physiological and clinical significance of the expression pattern of galectin-3 ligands to be established. This manuscript contains online supplemental material at http://www.jhc.org. Please visit this article online to view these materials.


Assuntos
Fosfatase Alcalina/genética , Galectina 3/genética , Proteínas Recombinantes de Fusão , Animais , Anticorpos Monoclonais , Linhagem Celular Tumoral , Proteínas de Escherichia coli/genética , Galectina 3/imunologia , Galectina 3/metabolismo , Glicoproteínas/metabolismo , Glicosilação , Humanos , Técnicas Imunoenzimáticas , Ligantes , Melanoma Experimental/metabolismo , Camundongos , Neoplasias/metabolismo , Oligossacarídeos/metabolismo , Ratos , Proteínas Recombinantes de Fusão/genética , Sarcoma Experimental/metabolismo , Sensibilidade e Especificidade , Análise Serial de Tecidos
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