In breast cancer, lipid metabolic alterations have been recognized as potential oncogenic stimuli that may promote malignancy. To investigate whether the oncogenic nature of lipogenesis closely depends on the overexpression of HER2 protooncogene, the normal breast cell line, HB4a, was transfected with HER2 cDNA to obtain HER2-overexpressing HB4aC5.2 cells. Both cell lines were treated with trastuzumab and docosahexaenoic acid. HER2 overexpression was accompanied by an increase in the expression of lipogenic genes involved in uptake (CD36), transport (FABP4), and storage (DGAT) of exogenous fatty acids (FA), as well as increased activation of “de novo” FA synthesis (FASN). We further investigate whether this lipogenesis reprogramming might be regulated by mTOR/PPARγ pathway. Inhibition of the mTORC1 pathway markers, p70S6 K1, SREBP1, and LIPIN1, as well as an increase in DEPTOR expression (the main inhibitor of the mTOR) was detected in HB4aC5.2. Based on these results, a PPARγ selective antagonist, GW9662, was used to treat both cells lines, and the lipogenic genes remained overexpressed in the HB4aC5.2 but not HB4a cells. DHA treatment inhibited all lipogenic genes (except for FABP4) in both cell lines yet only induced death in the HB4aC5.2 cells, mainly when associated with trastuzumab. Neither trastuzumab nor GW9662 alone was able to induce cell death. In conclusion, oncogenic transformation of breast cells by HER2 overexpression may require a reprogramming of lipogenic genetic that is independent of mTORC1 pathway and PPARγ activity. This reprogramming was inhibited by DHA.
2018) The invasive red palm mite, Raoiellaindica Hirst (Acari: Tenuipalpidae), in Brazil: range extension and arrival into the most threatened area, the Northeast Region, ABSTRACT Raoiella indica Hirst (Acari: tenuipalpidae), commonly known as the red palm mite (RPM), is an invasive polyphagous pest, which has emerged as a threat to agriculture in the Americas. In the Americas, the mite has not only spread quickly, but also greatly extended its host range in the new areas where it has been observed. We present here new records of the RPM in Brazilian states, with focus on its arrival into the most threatened area, the Northeast Region. Coconut and banana are important crops in this region of Brazil and represent the main threatened crops by this pest. These new records of RPM reinforce the idea that this species is already widely distributed throughout Brazil eight years after its introduction into the extreme North state of Roraima. Comments on the possible economic, social and environmental impacts are presented. ARTICLE HISTORY
Altered cell metabolism is a hallmark of cancer and critical for its development. Particularly, activation of one-carbon metabolism in tumor cells can sustain oncogenesis while contributing to epigenetic changes and metabolic adaptation during tumor progression. We assessed whether increased one-carbon metabolism activity is a metabolic feature of invasive ductal carcinoma (IDC). Differences in the metabolic profile between biopsies from IDC (n = 47) and its adjacent tissue (n = 43) and between biopsies from different breast cancer subtypes were assessed by gas spectrometry in targeted (Biocrates Life Science ®) and untargeted approaches, respectively. The metabolomics data were statistically treated using MetaboAnalyst 4.0, SIMCA P+ (version 12.01), Statistica 10 software and t test with p < 0.05. The Cancer Genome Atlas breast cancer dataset was also assessed to validate the metabolomic profile of IDC. Our targeted metabolomics analysis showed distinct metabolomics profiles between IDC and adjacent tissue, where IDC displayed a comparative enrichment of metabolites involved in one-carbon metabolism (serine, glycine, threonine, and methionine) and a predicted increase in the activity of pathways that receive and donate carbon units (i.e., folate, methionine, and homocysteine). In addition, the targeted and untargeted metabolomics analyses showed similar metabolomics profiles between breast cancer subtypes. The gene set enrichment analysis identified different transcription-related functions between IDC and non-tumor tissues that involved onecarbon metabolism. Our data suggest that one-carbon metabolism may be a central pathway in IDC and even in general breast tumors, representing a potential target for its treatment and prevention.
Medidas para o controle de Raoiella indica Hirst, 1924 infestando e causando prejuízos em cultivos de Cocos nucifera são escassas no Brasil. Visando fomentar programas de manejo desse ácaro na cultura do coqueiro, comparou-se a efetividade in vitro dos acaricidas abamectina, clorfenapir e fenpiroximato sobre fêmeas adultas de R. indica, de acordo com a dosagem recomendada para mortalidade de 80% de ácaros-praga. Avaliaram-se a mortalidade após 3, 6, 12, 24, 48 e 72 horas após aplicação, mortalidade acumulada e análise de sobrevivência das fêmeas. Com base na normalidade dos dados, foram utilizados Modelos Lineares Generalizados (GLM) e as médias comparadas pelo teste Tukey a 5% de probabilidade. Para os três parâmetros avaliados, abamectina foi o mais tóxico nas primeiras horas após aplicação, com o maior pico de mortalidade 6 horas após. Fenpiroximato mostrou-se eficiente com o passar do tempo, igualando-se à abamectina após 12 horas. Ambos ocasionaram mortalidade de 98% após 72 horas. A ação de clorfenapir foi mais tardia em relação aos demais acaricidas, contudo, foi o único que ocasionou 100% de mortalidade. Os três produtos mostraram-se eficientes no controle de R. indica em testes conduzidos em laboratório, no entanto, a abamectina mostrou-se tóxico logo nas seis primeiras horas após a aplicação, com eficiência de 85,42% sobre a mortalidade acumulada, sendo o produto com ação mais rápida no controle das fêmeas adultas de R. indica.
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