RESUMO
BACKGROUND: Delayed parasite clearance and, consequently, reduced efficacy of artemisinin-based combination therapies have been linked with Plasmodium falciparum K13 gene SNPs in Southeast Asia. In Africa, significantly prolonged clearance has not yet been observed and the presently restricted variation in parasite clearance cannot be explained by K13 polymorphisms. OBJECTIVES: Our aim was to study the in vivo pfK13 transcriptional response in patients treated with artemether-lumefantrine and explore whether the pfk13 transcripts can explain the patients' parasite clearance outcomes. PATIENTS AND METHODS: A total of 47 Tanzanian children with microscopically confirmed uncomplicated P. falciparum malaria were hospitalized and received artemether-lumefantrine treatment (clinical trial ID: NCT00336375). RNA was extracted from venous blood samples collected before treatment initiation and at five more timepoints after treatment. cDNA was synthesized and pfk13 transcripts measured by real-time PCR. RESULTS: A wide range of pfk13 transcript variation was observed throughout all timepoints after artemether-lumefantrine treatment. Taking parasite clearance data together with the pfk13 transcripts profile, we observed a negative correlation inferring that pfk13 down-regulation is associated with longer parasite clearance time. CONCLUSIONS: The findings suggest that a reduced PfK13 transcriptional response may represent a first step towards artemisinin tolerance/resistance.
Assuntos
Antimaláricos/uso terapêutico , Combinação Arteméter e Lumefantrina/uso terapêutico , Tolerância a Medicamentos , Expressão Gênica , Malária Falciparum/tratamento farmacológico , Plasmodium falciparum/efeitos dos fármacos , Proteínas de Protozoários/genética , Animais , Antimaláricos/farmacologia , Combinação Arteméter e Lumefantrina/farmacologia , Criança , Pré-Escolar , Feminino , Perfilação da Expressão Gênica , Humanos , Lactente , Malária Falciparum/parasitologia , Masculino , Tanzânia , Resultado do TratamentoRESUMO
Giant-cell bone tumors are a rare entity. Only 7.5 to 15% are malignant tumors and correspond to 0.5% of all primary malignant bone tumors. This case report has an unusual localization (ischium) for this kind of tumor (+/- 0.6%). The patient was treated with radiotherapy alone, because local extension of the disease would require very aggressive surgery with functional implications. Ten years after treatment, the patient is alive without clinical evidence of disease, and without functional impairments.
Assuntos
Neoplasias Ósseas/diagnóstico , Tumor de Células Gigantes do Osso/diagnóstico , Ísquio , Neoplasias Ósseas/radioterapia , Seguimentos , Tumor de Células Gigantes do Osso/radioterapia , Humanos , Ísquio/diagnóstico por imagem , Ísquio/patologia , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Dosagem Radioterapêutica , Tomografia Computadorizada por Raios XRESUMO
Angiosarcoma of the breast is a rare but highly malignant neoplasm of vascular origin. The median survival in previously reported cases is 22 months. The treatment of choice is simple mastectomy. Although the value of irradiation or chemotherapy as the only form of treatment is limited, their role as adjuvant therapy should be explored. One case is presented and a review of the literature is made.
