Nanoformulation shows cytotoxicity against glioblastoma cell lines and antiangiogenic activity in chicken chorioallantoic membrane

Glioblastoma (GB) is a histological and genetically heterogeneous brain tumor that is highly proliferative and vascularized. The prognosis is poor with currently available treatment. In this study, we evaluated the cytotoxicity and antiangiogenic activity of doxorubicin-loaded-chitosan-coated-arginylglycylaspartic acid-functionalized-poly(ε-caprolactone)-alpha bisabolol-LNC (AB-DOX-LNC-L-C-RGD). The nanoformulation was prepared by self-assembling followed by interfacial reactions, physicochemically characterized and evaluated in vitro against GB cell lines (U87MG and U138MG) and in vivo using the chicken chorioallantoic membrane assay (CAM). Spherical shape nanocapsules had a hydrodynamic mean diameter of 138 nm, zeta potential of +13.4 mV, doxorubicin encapsulation of 65%, and RGD conjugation of 92%. After 24 h of treatment (U87MG and U138MG), the median inhibition concentrations (IC50) were 520 and 490 nmol L−1 doxorubicin-equivalent concentrations, respectively. The treatment induced antiproliferative activity with S-phase cell-cycle arrest and apoptosis in the GB cells. Furthermore, after 48 h of exposure, evaluation of antiangiogenic activity (CAM) showed that the relative vessel growth following treatment with the nanocapsules was 5.4 times lower than that with the control treatment. The results support the therapeutic potential of the nanoformulation against GB and, thereby, pave the way for future preclinical studies

Phosphatidylinositol 3-kinase/AKT pathway inhibition by doxazosin promotes glioblastoma cells death, upregulation of p53 and triggers low neurotoxicity

Glioblastoma is the most frequent and malignant brain tumor. Treatment includes chemotherapy with temozolomide concomitant with surgical resection and/or irradiation. However, a number of cases are resistant to temozolomide, as well as the human glioblastoma cell line U138-MG. We investigated doxazosin’s (an antihypertensive drug) activity against glioblastoma cells (C6 and U138-MG) and its neurotoxicity on primary astrocytes and organoptypic hippocampal cultures. For this study, the following methods were used: citotoxicity assays, flow cytometry, western-blotting and confocal microscopy. We showed that doxazosin induces cell death on C6 and U138-MG cells. We observed that doxazosin’s effects on the PI3K/Akt pathway were similar as LY294002 (PI3K specific inhibitor). In glioblastoma cells treated with doxasozin, Akt levels were greatly reduced. Upon examination of activities of proteins downstream of Akt we observed upregulation of GSK-3β and p53. This led to cell proliferation inhibition, cell death induction via caspase-3 activation and cell cycle arrest at G0/G1 phase in glioblastoma cells. We used in this study Lapatinib, a tyrosine kinase inhibitor, as a comparison with doxazosin because they present similar chemical structure. We also tested the neurocitotoxicity of doxazosin in primary astrocytes and organotypic cultures and observed that doxazosin induced cell death on a small percentage of non-tumor cells. Aggressiveness of glioblastoma tumors and dismal prognosis require development of new treatment agents. This includes less toxic drugs, more selective towards tumor cells, causing less damage to the patient. Therefore, our results confirm the potential of doxazosin as an attractive therapeutic antiglioma agent

Dietoterapia chinesa no tratamento de suporte ao paciente geriátrico

Os avanços na medicina veterinária durante as últimas décadas proporcionaram um aumento significativo na expectativa de vida dos animais de companhia, provocando um crescimento no número de pacientes geriátricos atendidos pelos médicos veterinários. O tratamento das doenças nestes pacientes deve ser cauteloso, pois muitos fármacos apresentam maior toxicidade nos animais idosos. Neste cenário, a Medicina Tradicional Chinesa (MTC) vem apresentando um papel cada vez mais importante como terapia complementar na medicina veterinária, visto que seus efeitos colaterais são mínimos, enquanto os efeitos terapêuticos são bastante eficazes. A dietoterapia era considerada o primeiro passo no tratamento das enfermidades. Ainda hoje, a dietoterapia é utilizada com as funções de agregar qualidade de vida, prevenir de doenças e tratar enfermidades, sejam elas agudas ou crônicas. Este trabalho abordará algumas das principais enfermidades que acometem animais idosos a fim de propor alimentos que possam ser utilizados como suporte ao tratamento convencional (dietoterapia de suporte), visto que apresenta inúmeros benefícios, minimizando os efeitos colaterais de medicamentos, potencializando os efeitos desejados das terapias em curso e melhorando a qualidade de vida do paciente geriátrico.The advances in veterinary medicine during the past decades have provided a significant increase in companion animals’ life expectancy, causing an increase in the geriatric patient rate in the veterinary’s routine. The treatment of diseases in these animals should be cautious, because drugs are usually more toxic for elderly patients. In this scenario, Chinese Traditional Medicine (TCM) has an important role as a complementary therapy in veterinary medicine, since its side effects are minimal, while its therapeutic effects are very effective. In ancient China, food therapy was considered the first step in the treatment of illnesses. Currently, Chinese food therapy is used to aggregate quality of life, prevent diseases and treat illnesses, whether they are acute or chronic. This paper will discuss some of the most frequent illnesses that afflict the geriatric patient in order to propose nourishments that can be offered as a support to the conventional treatment (support food therapy), since it provides numerous benefits such as: ease most drug’s side effects, potentiate the desired effects from the conventional therapies and increasing the geriatric patient’s quality of life

Dietoterapia chinesa no tratamento de suporte ao paciente geriátrico

Os avanços na medicina veterinária durante as últimas décadas proporcionaram um aumento significativo na expectativa de vida dos animais de companhia, provocando um crescimento no número de pacientes geriátricos atendidos pelos médicos veterinários. O tratamento das doenças nestes pacientes deve ser cauteloso, pois muitos fármacos apresentam maior toxicidade nos animais idosos. Neste cenário, a Medicina Tradicional Chinesa (MTC) vem apresentando um papel cada vez mais importante como terapia complementar na medicina veterinária, visto que seus efeitos colaterais são mínimos, enquanto os efeitos terapêuticos são bastante eficazes. A dietoterapia era considerada o primeiro passo no tratamento das enfermidades. Ainda hoje, a dietoterapia é utilizada com as funções de agregar qualidade de vida, prevenir de doenças e tratar enfermidades, sejam elas agudas ou crônicas. Este trabalho abordará algumas das principais enfermidades que acometem animais idosos a fim de propor alimentos que possam ser utilizados como suporte ao tratamento convencional (dietoterapia de suporte), visto que apresenta inúmeros benefícios, minimizando os efeitos colaterais de medicamentos, potencializando os efeitos desejados das terapias em curso e melhorando a qualidade de vida do paciente geriátrico.The advances in veterinary medicine during the past decades have provided a significant increase in companion animals’ life expectancy, causing an increase in the geriatric patient rate in the veterinary’s routine. The treatment of diseases in these animals should be cautious, because drugs are usually more toxic for elderly patients. In this scenario, Chinese Traditional Medicine (TCM) has an important role as a complementary therapy in veterinary medicine, since its side effects are minimal, while its therapeutic effects are very effective. In ancient China, food therapy was considered the first step in the treatment of illnesses. Currently, Chinese food therapy is used to aggregate quality of life, prevent diseases and treat illnesses, whether they are acute or chronic. This paper will discuss some of the most frequent illnesses that afflict the geriatric patient in order to propose nourishments that can be offered as a support to the conventional treatment (support food therapy), since it provides numerous benefits such as: ease most drug’s side effects, potentiate the desired effects from the conventional therapies and increasing the geriatric patient’s quality of life