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Metronomic treatment in immunocompetent preclinical GL261 glioblastoma: effects of cyclophosphamide and temozolomide
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Laura Ferrer‐Font Nuria Arias‐Ramos Silvia Lope‐Piedrafita Margarida Julià‐Sapé Martí Pumarola Carles Arús Ana Paula Candiota 《NMR in biomedicine》2017,30(9)
Glioblastoma (GBM) causes poor survival in patients even when applying aggressive treatment. Temozolomide (TMZ) is the standard chemotherapeutic choice for GBM treatment, but resistance always ensues. In previous years, efforts have focused on new therapeutic regimens with conventional drugs to activate immune responses that may enhance tumor regression and prevent regrowth, for example the “metronomic” approaches. In metronomic scheduling studies, cyclophosphamide (CPA) in GL261 GBM growing subcutaneously in C57BL/6 mice was shown not only to activate antitumor CD8+ T‐cell response, but also to induce long‐term specific T‐cell tumor memory. Accordingly, we have evaluated whether metronomic CPA or TMZ administration could increase survival in orthotopic GL261 in C57BL/6 mice, an immunocompetent model. Longitudinal in vivo studies with CPA (140 mg/kg) or TMZ (range 140–240 mg/kg) metronomic administration (every 6 days) were performed in tumor‐bearing mice. Tumor evolution was monitored at 7 T with MRI (T2‐weighted, diffusion‐weighted imaging) and MRSI‐based nosological images of response to therapy. Obtained results demonstrated that both treatments resulted in increased survival (38.6 ± 21.0 days, n = 30) compared with control (19.4 ± 2.4 days, n = 18). Best results were obtained with 140 mg/kg TMZ (treated, 44.9 ± 29.0 days, n = 12, versus control, 19.3 ± 2.3 days, n = 12), achieving a longer survival rate than previous group work using three cycles of TMZ therapy at 60 mg/kg (33.9 ± 11.7 days, n = 38). Additional interesting findings were, first, clear edema appearance during chemotherapeutic treatment, second, the ability to apply the semi‐supervised source analysis previously developed in our group for non‐invasive TMZ therapy response monitoring to detect CPA‐induced response, and third, the necropsy findings in mice cured from GBM after high TMZ cumulative dosage (980–1400 mg/kg), which demonstrated lymphoma incidence. In summary, every 6 day administration schedule of TMZ or CPA improves survival in orthotopic GL261 GBM with respect to controls or non‐metronomic therapy, in partial agreement with previous work on subcutaneous GL261. 相似文献
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Melatonin enhances neural stem cell differentiation and engraftment by increasing mitochondrial function
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![点击此处可从《Journal of pineal research》网站下载免费的PDF全文](/ch/ext_images/free.gif)
Miguel Mendivil‐Perez Viviana Soto‐Mercado Ana Guerra‐Librero Beatriz I. Fernandez‐Gil Javier Florido Ying‐Qiang Shen Miguel A. Tejada Vivian Capilla‐Gonzalez Iryna Rusanova José M. Garcia‐Verdugo Darío Acuña‐Castroviejo Luis Carlos López Carlos Velez‐Pardo Marlene Jimenez‐Del‐Rio José M. Ferrer Germaine Escames 《Journal of pineal research》2017,63(2)
Neural stem cells (NSCs) are regarded as a promising therapeutic approach to protecting and restoring damaged neurons in neurodegenerative diseases (NDs) such as Parkinson's disease and Alzheimer's disease (PD and AD, respectively). However, new research suggests that NSC differentiation is required to make this strategy effective. Several studies have demonstrated that melatonin increases mature neuronal markers, which reflects NSC differentiation into neurons. Nevertheless, the possible involvement of mitochondria in the effects of melatonin during NSC differentiation has not yet been fully established. We therefore tested the impact of melatonin on NSC proliferation and differentiation in an attempt to determine whether these actions depend on modulating mitochondrial activity. We measured proliferation and differentiation markers, mitochondrial structural and functional parameters as well as oxidative stress indicators and also evaluated cell transplant engraftment. This enabled us to show that melatonin (25 μM) induces NSC differentiation into oligodendrocytes and neurons. These effects depend on increased mitochondrial mass/DNA/complexes, mitochondrial respiration, and membrane potential as well as ATP synthesis in NSCs. It is also interesting to note that melatonin prevented oxidative stress caused by high levels of mitochondrial activity. Finally, we found that melatonin enriches NSC engraftment in the ND mouse model following transplantation. We concluded that a combined therapy involving transplantation of NSCs pretreated with pharmacological doses of melatonin could efficiently restore neuronal cell populations in PD and AD mouse models depending on mitochondrial activity promotion. 相似文献
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Catherine J. Goodhue Rita V. Burke Rizaldy R. Ferrer Nikunj K. Chokshi Fred Dorey Jeffrey S. Upperman 《Journal of pediatric health care》2012,26(4):e7-e20
ObjectiveThe objective of this study was to examine factors associated with pediatric nurse practitioners (PNPs) reporting to work in the event of a disaster.MethodsAn anonymous national survey of PNPs was conducted. Several domains were explored, including demographics, personal preparedness plans, disaster training, prior disaster experience, and likelihood of responding in the event of a disaster. A logistic regression analysis was conducted to determine which factors were associated with the respondent’s likelihood of responding in the event of a disaster.ResultsFactors associated with increased likelihood of responding included gender (being a male PNP), military experience, and disaster training. The most significant factor associated with an increased likelihood of responding to work during a disaster was having a specified role in the workplace disaster plan. PNPs with a specified role were three times more likely to respond than were those without a specified role.ConclusionsPNPs are health care workers with advanced skill sets. This untapped resource is available to provide care for a vulnerable population: our children. Disaster planners should explore the possibility of utilizing these highly skilled health care workers in their disaster plans. 相似文献
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Luis Felipe Casado José Ángel Hernández Isidro Jarque María Echave Miguel Angel Casado Antonio Castro 《European journal of haematology》2018,100(3):264-272
Objective
To evaluate the incremental cost‐utility ratio (ICUR) of idelalisib in combination with rituximab (IR) versus rituximab monotherapy (R) in the treatment of patients with relapsed or refractory (R/R) chronic lymphocytic leukaemia (CLL), from the Spanish National Health System (NHS) perspective.Methods
A partitioned survival Markov model for a lifetime horizon (30 years) was developed to estimate costs (€, 2016) and quality‐adjusted life years (QALY) with IR and R. Initial cohort included patients with CLL receiving a second or subsequent line (2L) of treatment with IR or R. Survival data were based on CLL clinical trial. Drug, administration, monitoring, adverse events and clinical management of CLL costs were included in the model. Costs and outcomes were discounted using a 3% annually. Deterministic and probabilistic sensitivity analyses (PSA) were performed.Results
Compared to R, 2L IR treatment resulted in QALY gain of 3.147 (4.965 versus 1.818). Total costs were €118 254 for IR versus €23 874 for R. ICUR was €29 990/QALY gained with IR versus R. In the PSA, IR was cost‐effective in 78% of iterations using a threshold of €45 000/QALY.Conclusion
IR can be considered a cost‐effective treatment compared to R, in the treatment of R/R CLL patients for the Spanish NHS. 相似文献58.
Does flavoured dentifrice increase fluoride intake compared with regular toothpaste in children? A systematic review and meta‐analysis
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Thiago Isidro Vieira Adrielle Mangabeira Adílis Kalina Alexandria Daniele Masterson T. P. Ferreira Tatiana Kelly da Silva Fidalgo Ana Maria Gondim Valença Lucianne Cople Maia 《International journal of paediatric dentistry / the British Paedodontic Society [and] the International Association of Dentistry for Children》2018,28(3):279-290
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