35 research outputs found
Somatic LKB1 Mutations Promote Cervical Cancer Progression
Human Papilloma Virus (HPV) is the etiologic agent for cervical cancer. Yet, infection with HPV is not sufficient to cause cervical cancer, because most infected women develop transient epithelial dysplasias that spontaneously regress. Progression to invasive cancer has been attributed to diverse host factors such as immune or hormonal status, as no recurrent genetic alterations have been identified in cervical cancers. Thus, the pressing question as to the biological basis of cervical cancer progression has remained unresolved, hampering the development of novel therapies and prognostic tests. Here we show that at least 20% of cervical cancers harbor somatically-acquired mutations in the LKB1 tumor suppressor. Approximately one-half of tumors with mutations harbored single nucleotide substitutions or microdeletions identifiable by exon sequencing, while the other half harbored larger monoallelic or biallelic deletions detectable by multiplex ligation probe amplification (MLPA). Biallelic mutations were identified in most cervical cancer cell lines; HeLa, the first human cell line, harbors a homozygous 25 kb deletion that occurred in vivo. LKB1 inactivation in primary tumors was associated with accelerated disease progression. Median survival was only 13 months for patients with LKB1-deficient tumors, but >100 months for patients with LKB1-wild type tumors (Pâ=â0.015, log rank test; hazard ratioâ=â0.25, 95% CIâ=â0.083 to 0.77). LKB1 is thus a major cervical tumor suppressor, demonstrating that acquired genetic alterations drive progression of HPV-induced dysplasias to invasive, lethal cancers. Furthermore, LKB1 status can be exploited clinically to predict disease recurrence
Usage patterns, health, and nutritional status of long-term multiple dietary supplement users: a cross-sectional study
© 2007 Block et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution Licens
A Budget Impact Model for Paclitaxel-eluting Stent in Femoropopliteal Disease in France
A half-marathon and a marathon run induce oxidative DNA damage, reduce antioxidant capacity to protect DNA against damage and modify immune function in hobby runners
Eletroestimulação muscular: alternativa de tratamento coadjuvante para pacientes com doença arterial obstrutiva periférica Muscle electrostimulation: alternative adjuvant treatment to patients with peripheral arterial obstructive disease
A doença arterial perifĂ©rica faz parte de um grupo de patologias vasculares que evolui de forma lenta e progressiva. A proposta deste artigo foi avaliar, por meio de revisĂŁo bibliogrĂĄfica, os possĂveis benefĂcios da eletroestimulação crĂŽnica como tratamento coadjuvante para pacientes arteriopatas. De acordo com a literatura analisada, concluĂmos que a eletroestimulação Ă© capaz de provocar alteraçÔes importantes no perfil metabĂłlico das fibras musculares, convertendo-as do tipo II para o tipo I, o que induz o crescimento capilar, a densidade capilar e o suprimento de oxigĂȘnio. Desta forma, este recurso terapĂȘutico aumenta a capacidade aerĂłbica oxidativa e a resistĂȘncia Ă fadiga dos mĂșsculos isquĂȘmicos. Assim, a eletroestimulação Ă© mais um recurso terapĂȘutico capaz de melhorar a habilidade para caminhar destes pacientes, diminuindo gastos com cirurgias de revascularização e complicaçÔes maiores.<br>Peripheral arterial disease is included in a group of vascular diseases whose evolution is slow and progressive. This article aimed at performing a literature review to evaluate the benefits of chronic electrostimulation as adjuvant treatment for arteriopathic patients. Based on the literature, we concluded that electrostimulation can generate important changes in the metabolic profile of muscle fibers, switching them from type II to type I, which leads to capillary increase, capillary density and suppression of oxygen. Therefore, this therapeutic resource increases aerobic oxidative capacity and ischemic muscle resistance to fatigue. Thus, electrostimulation is another therapeutic option able to improve these patients' walking ability, reducing expenses related to revascularization surgeries and major complications