Interaction between lung cancer cells and astrocytes via specific inflammatory cytokines in the microenvironment of brain metastasis

The incidence of brain metastasis is increasing, however, little is known about molecular mechanism responsible for lung cancer-derived brain metastasis and their development in the brain. In the present study, brain pathology was examined in an experimental model system of brain metastasis as well as in human brain with lung cancer metastasis. In an experimental model, after 3–6 weeks of intracardiac inoculation of human lung cancer-derived (HARA-B) cells in nude mice, wide range of brain metastases were observed. The brain sections showed significant increase in glial fibrillary acidic protein (GFAP)-positive astrocytes around metastatic lesions. To elucidate the role of astrocytes in lung cancer proliferation, the interaction between primary cultured mouse astrocytes and HARA-B cells was analyzed in vitro. Co-cultures and insert-cultures demonstrated that astrocytes were activated by tumor cell-oriented factors; macrophage migration inhibitory factor (MIF), interleukin-8 (IL-8) and plasminogen activator inhibitor-1 (PAI-1). Activated astrocytes produced interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α) and interleukin-1 β (IL-1β), which in turn promoted tumor cell proliferation. Semi-quantitative immunocytochemistry showed that increased expression of receptors for IL-6 and its subunits gp130 on HARA-B cells. Receptors for TNF-α and IL-1β were also detected on HARA-B cells but down-regulated after co-culture with astrocytes. Insert-culture with astrocytes also stimulated the proliferation of other lung cancer-derived cell lines (PC-9, QG56, and EBC-1). These results suggest that tumor cells and astrocytes stimulate each other and these mutual relationships may be important to understand how lung cancer cells metastasize and develop in the brain

Infantile zinc deficiency: Association with autism spectrum disorders

Elucidation of the pathogenesis and effective treatment of autism spectrum disorders is one of the challenges today. In this study, we examine hair zinc concentrations for 1,967 children with autistic disorders (1,553 males and 414 females), and show considerable association with zinc deficiency. Histogram of hair zinc concentration was non-symmetric with tailing in lower range, and 584 subjects were found to have lower zinc concentrations than −2 standard deviation level of its reference range (86.3–193ppm). The incidence rate of zinc deficiency in infant group aged 0–3 year-old was estimated 43.5 % in male and 52.5 % in female. The lowest zinc concentration of 10.7 ppm was detected in a 2-year-old boy, corresponding to about 1/12 of the control mean level. These findings suggest that infantile zinc deficiency may epigenetically contribute to the pathogenesis of autism and nutritional approach may yield a novel hope for its treatment and prevention

Breaking the cycle: how I manage difficult atopic dermatitis Romper o ciclo: minha conduta em casos difíceis de dermatite atópica

This review summarizes the general approach and philosophy of managing difficult atopic dermatitis. There are as many regimens as there are physicians, but too many fail to provide patients with adequate relief. This leads to the wasteful alternative - an allergy-seeking behavior that makes caring for these patients even more complicated. If we, as dermatologists, provide rational counseling on prevention and skin care along with effective, stable, anti-inflammatory therapy, our patients may stop seeking irrational approaches. The new flood of information relating to epidermal barrier provides a basis for seeking and treating xerotic conditions earlier during infancy with the hope that the increasing problems with atopic dermatitis and asthma may be lessened with simple and safe measures.<br>Esta revisão resume a abordagem geral e a filosofia na conduta de casos difíceis de dermatite atópica. Existe uma variedade de tratamentos, assim como de médicos, mas muitos falham e não propiciam um alívio adequado aos pacientes, o que leva a uma alternativa dispendiosa, ou seja, um atitude que visa procurar alergias e complica ainda mais o tratamento desses pacientes. Se nós, como dermatologistas, oferecermos um aconselhamento racional sobre prevenção e cuidados com a pele, junto com uma terapia antiinflamatória eficaz e estável, nossos pacientes irão parar de procurar abordagens irracionais. O novo fluxo de informações sobre a barreira epidérmica propicia uma base para investigar e tratar as doenças xeróticas em uma fase mais precoce durante o primeiro ano de vida, com a esperança de que os problemas crescentes relacionados à dermatite atópica e asma possam ser atenuados com medidas simples e seguras