Efficacy of monoterpene perillyl alcohol upon survival rate of patients with recurrent glioblastoma.

PURPOSE: The monoterpene perillyl alcohol (POH) a Ras inhibitor with potential capacity to arrest gliomagenesis is being used in a phase I/II clinical trial in adults with recurrent malignant glioma. The present study aimed to investigate the efficacy of intranasal administration of monoterpene POH upon survival rate of patients with recurrent glioblastoma (GBM) in comparison with historical control group of GBM patients. PATIENTS AND METHODS: It was included 89 adults with recurrent GBM receiving daily intranasal administration of 440 mg POH and 52 matched GBM patients as historical control untreated group only with supportive treatment. RESULTS: Patients with recurrent primary GBM treated with POH survived significantly longer (log rank test, P < 0.0001) than untreated group. Patients with recurrent primary GBM in deep location survived significantly longer than with lobar location (log rank test, P < 0.0001). Median survival rate of secondary GBM was 11.2 months, longer (log rank test, P = 0.0366) than primary GBM (5.9 months). Radiographic improvement and reduction of corticosteroid dosage (36%) further associated with a delay towards progression. CONCLUSION: Intranasal administration of POH increased the overall survival of patients with recurrent GBM in comparison with historical untreated controls, but especially patients with secondary GBM and primary GBM with tumor localized in deep regions of the brain. The side effects of POH treatment were almost nonexistent, even in patients treated for over 4 years.

Herpes genital / Genital herpes

O herpes genital é uma doença infectocontagiosa sujeita a recidivas, tendo como agente etiológico duas cepas diferentes do vírus herpes simples (HSV), o tipo 1 (HSV-1) e o tipo 2 (HSV-2). A grande maioria dos casos de herpes genital é causada pelo HSV-2, embora a prevalência do HSV-1 esteja em ascensão, principalmente na população jovem e devido à prática de sexo oral. A manifestação clínica pode ser primária ou recorrente, esta última acontecendo por reativação viral. O diagnóstico é feito pelas características clínicas associadas às confirmações laboratoriais da infecção. Diversos estudos clínicos e epidemiológicos demonstram a sinergia entre herpes genital e aids. Na gravidez, a grande preocupação acerca da infecção pelo HSV refere-se à morbidadee à mortalidade associadas à infecção neonatal. Atualmente não existe nenhum tratamento eficaz na cura do herpes genital, mas alguns medicamentos antivirais são capazes de diminuir o tempo da doença e prevenir as erupções. A maioria dos esforços para combater a infecção herpética genital concentrase no desenvolvimento de vacinas.

Genital herpes is an infectious disease subject to recurrent crises, with the etiologic agent of two different strains of herpes simplex virus (HSV), the type 1 (HSV-1) and type 2 (HSV-2). The vast majority of genital herpes cases is caused by HSV-2, although the prevalence of HSV-1 is on the rise, especially in young population and due to oral sex. The clinical manifestations may be primary or recurrent, the latter going on viral reactivation. The diagnosis is made by the clinical characteristics associated with laboratory confirmation of infection. Several epidemiological and clinical studies demonstrate the synergybetween genital herpes and aids. In pregnancy, the major concern about HSV infection refers to the morbidity and mortality associated with neonatal infection. Currently, there is no treatment capable of curing genital herpes, but some antiviral drugs are able to decrease the duration of the disease and prevent flares. Most efforts to combat genital herpes infection are focused on vaccine development.

Correlation of tumor topography and peritumoral edema of recurrent malignant gliomas with therapeutic response to intranasal administration of perillyl alcohol.

BACKGROUND: The aim of this study was to establish a correlation of tumor topography and peritumoral brain edema with the therapeutic response to intranasal administration of perillyl alcohol (POH) in a cohort of patients with recurrent malignant gliomas. METHODS: The retrospective study reviewed clinical and neuroradiological data from patients with recurrent malignant gliomas who received intranasal daily administration of POH 440 mg. The following parameters were assessed: demographic characteristics, initial symptoms, overall survival, tumor topography and tumor size, presence of midline shift and extent of peritumoral edema. Statistical analysis was carried out with log rank tests and overall survival as assessed by Kaplan-Meier method including 95% confidence intervals. RESULTS: A cohort of 67 patients included 52 (78%) with glioblastoma (GBM), ten (15%) with anaplastic astrocytoma (AA) and five (7%) with anaplastic oligodendroglioma (AO). Accordingly to tumor topography lobar localization was present in all (5/5) AO; eight (8/10) and 41 GBM patients whereas in the basal ganglia two AA and 11 GBM patients. It was also observed a relation between the tumor size and area of peritumoral brain edema (PTBE). Patients with good therapeutic response showed reduction of tumor size and PTBE area, but poor prognosis was associated with lack of response to treatment and persistence of high PTBE. Patients with tumor in the basal ganglia survived significantly longer than those with lobar gliomas (log rank test, p = 0.0003). Presence of midline shift (>1 cm) was a statistically significant risk factor for shorter survival (log rank test, p = 0.0062) CONCLUSIONS: This study suggests that: (1) patients with recurrent gliomas with localization in the basal ganglia survive significantly longer than those with tumors at lobar localization; (2) presence of PTBE contributes to symptoms, likely to be implicated in the morbidity and invading potential of malignant gliomas. These findings support the theory that interaction between glioma cells at distinct brain microenvironment can influence the oncobiological behavior of glioma cells and ultimately to the prognosis.

Análise de metaloproteases de matriz extracelular como indicador prognóstico nos gliomas malignos / Analysis of matrix metalloproteinase as prognostic indicator in malignant gliomas

Introdução: Metaloproteases de matriz extracelular(MMP) são enzimas proteolíticas sintetizadas na fase de fenótipo mais agressivo dos gliomas malignos, degradando proteínas da matriz extracelular,ocasionando ruptura da barreira hematoencefálica e contribuindo para a resposta neuroinflamatória,angiogênese e migração.Estudos mostram expressão de gelatinase A(MMP-2)proeminentemente nas células gliais tumorais,com pouca expressão na microvasculatura,enquanto expressão de gelatinase B(MMP-9)é proeminente na microvasculatrua, com porco sinal nas células tumorais.Objetivo:Neste estudo analisamos amostras de soro de 34 pacientes com gliomas malignos recidivos,antes e durante o tratamento com álcool perílico por via inalatória para determinar se a expressão de MMP poderia ser usada como indicador prognóstico.Métodos:A atividade gelatinade (MMP-2, MMP-9)nas amostras de soro foi determinada por zimografia e a atividade enzimática relativa foi determinada utilizando-se programa de análise densitométrica.Os valores foram correlacionados com exames de imagem e sobrevida dos pacientes. Resultados:Os resultados obtidos em nosso estudo evidenciaram que os pacientes com gliomas malignos apresentaram aumento da expressão de MMP-2 e MMP-9 quando comparados com pacientes saudáveis.Expressão aumentada de MMP-2 foi proporcional à progressão tumoral,sobrevida desfavorável e área de edema peritumoral.Conclusão:Esses resultados indicam proporcionalidade entre a expressão de MMP-2 e a malignidade dos gliomas, sugerindo seu emprego como indicador prognóstico para recorrência tumoral pós-operatória e sobrevida desfavorável dos pacientes.