Bone Metastases: An Overview Macedo, Filipa; Ladeira, Katia; Pinho, Filipa ...
Oncology Reviews,
05/2017, Letnik:
11, Številka:
1
Journal Article, Book Review
Recenzirano
Odprti dostop
Bone is a frequent site of metastases and typically indicates a short-term prognosis in cancer patients. Once cancer has spread to the bones it can rarely be cured, but often it can still be treated ...to slow its growth. The majority of skeletal metastases are due to breast and prostate cancer. Bone metastasis is actually much more common than primary bone cancers, especially in adults. The diagnosis is based on signs, symptoms and imaging. New classes of drugs and new interventions are given a better quality of life to these patients and improved the expectancy of life. It is necessary a multidisciplinary approach to treat patients with bone metastasis. In this paper we review the types, clinical approach and treatment of bone metastases.
Background & Aims There has not been a broad analysis of the combined effects of altered activities of microRNAs (miRNAs) in pancreatic ductal adenocarcinoma (PDAC) cells, and it is unclear how these ...might affect tumor progression or patient outcomes. Methods We combined data from miRNA and messenger RNA (mRNA) expression profiles and bioinformatic analyses to identify an miRNA−mRNA regulatory network in PDAC cell lines (PANC-1 and MIA PaCa-2) and in PDAC samples from patients. We used this information to identify miRNAs that contribute most to tumorigenesis. Results We identified 3 miRNAs (MIR21, MIR23A, and MIR27A) that acted as cooperative repressors of a network of tumor suppressor genes that included PDCD4, BTG2, and NEDD4L. Inhibition of MIR21, MIR23A, and MIR27A had synergistic effects in reducing proliferation of PDAC cells in culture and growth of xenograft tumors in mice. The level of inhibition was greater than that of inhibition of MIR21 alone. In 91 PDAC samples from patients, high levels of a combination of MIR21, MIR23A, and MIR27A were associated with shorter survival times after surgical resection. Conclusions In an integrated data analysis, we identified functional miRNA−mRNA interactions that contribute to growth of PDACs. These findings indicate that miRNAs act together to promote tumor progression; therapeutic strategies might require inhibition of several miRNAs.
In the advanced stages of illness, patients often face challenging decisions regarding their treatment and overall medical care. Terminal ill patients are commonly affected by infections. However, in ...palliative care, the use of antimicrobials can be an ethical dilemma. Deciding whether to treat, withhold, or withdraw the antimicrobial treatment for an infection can be difficult. Antimicrobial administration can lead to adverse outcomes but the two main benefits, longer survival and symptom relief, are the main reasons why physicians prescribe antimicrobial when treating terminally ill patients. For the patient who has an irreversible advanced heart or lung disease, or an advanced dementia, or a metastatic cancer, it is easier the decision of withholding mechanical ventilation, tube feeding, and dialysis than antibiotherapy. To characterize infections, agents, and their treatments in palliative care, we conducted a review of the literature. We also included some tips to help health professionals to guide their clinical approach.
Here, we show that miR‐515‐5p inhibits cancer cell migration and metastasis. RNA‐seq analyses of both oestrogen receptor receptor‐positive and receptor‐negative breast cancer cells overexpressing ...miR‐515‐5p reveal down‐regulation of NRAS, FZD4, CDC42BPA, PIK3C2B and MARK4 mRNAs. We demonstrate that miR‐515‐5p inhibits MARK4 directly 3′ UTR interaction and that MARK4 knock‐down mimics the effect of miR‐515‐5p on breast and lung cancer cell migration. MARK4 overexpression rescues the inhibitory effects of miR‐515‐5p, suggesting miR‐515‐5p mediates this process through MARK4 down‐regulation. Furthermore, miR‐515‐5p expression is reduced in metastases compared to primary tumours derived from both in vivo xenografts and samples from patients with breast cancer. Conversely, miR‐515‐5p overexpression prevents tumour cell dissemination in a mouse metastatic model. Moreover, high miR‐515‐5p and low MARK4 expression correlate with increased breast and lung cancer patients' survival, respectively. Taken together, these data demonstrate the importance of miR‐515‐5p/MARK4 regulation in cell migration and metastasis across two common cancers.
Synopsis
miR‐515‐5p inhibits cancer progression, cell migration and metastasis through its direct target MARK4, a regulator of the cytoskeleton and cell motility. Moreover, reduced miR‐515‐5p and increased MARK4 levels in metastatic lung and breast cancer correlate with poor patient prognosis.
MARK4 down‐regulation promotes microtubule polymerisation.
Increased cell spreading downstream of miR‐515‐5p overexpression or MARK4 silencing hinders cell motility and invasiveness.
miR‐515‐5p overexpression or MARK4 silencing prevent organ colonisation by circulating tumour cells.
MARK4 inhibitors may represent novel therapeutic agents to control cancer dissemination.
miR‐515‐5p inhibits cancer progression, cell migration and metastasis through its direct target MARK4, a regulator of the cytoskeleton and cell motility. Moreover, reduced miR‐515‐5p and increased MARK4 levels in metastatic lung and breast cancer correlate with poor patient prognosis.
Sphingosine kinase 1 (SK1) plays an important role in estrogen-dependent breast tumorigenesis, but its regulation is poorly understood. A subset of microRNAs (miRNA, miR) is regulated by estrogen and ...contributes to cellular proliferation and cancer progression. Here, we describe that miR-515-5p is transcriptionally repressed by estrogen receptor α (ERα) and functions as a tumor suppressor in breast cancer. Its downregulation enhances cell proliferation and estrogen-dependent SK1 activity, mediated by a reduction of miR-515-5p posttranscriptional repression. Enforced expression of miR-515-5p in breast cancer cells causes a reduction in SK1 activity, reduced cell proliferation, and the induction of caspase-dependent apoptosis. Conversely, opposing effects occur with miR-515-5p inhibition and by SK1 silencing. Notably, we show that estradiol (E2) treatment downregulates miR-515-5p levels, whereas the antiestrogen tamoxifen causes a decrease in SK1, which is rescued by silencing miR-515-5p. Analysis of chromatin immunoprecipitation sequencing (ChIP-Seq) data reveals that miR-515-5p suppression is mediated by a direct interaction of ERα within its promoter. RNA-sequencing (RNA-Seq) analysis of breast cancer cells after overexpressing miR-515-5p indicates that it partly modulates cell proliferation by regulating the Wnt pathway. The clinical implications of this novel regulatory system are shown as miR-515-5p is significantly downregulated in ER-positive (n = 146) compared with ER-negative (n = 98) breast cancers. Overall, we identify a new link between ERα, miR-515-5p, proliferation, and apoptosis in breast cancer tumorigenesis.
Resumo Neste artigo analisamos os regressos da emigração portuguesa a Portugal numa perspetiva histórica, com base na literatura científica de maioria portuguesa produzida desde os anos 1980 sobre o ...tema. Com este conjunto dos trabalhos disponíveis é possível reconstituir o padrão dos regressos através do volume contabilizado nos censos (ou de outras formas), conhecer perfis de regressados e avaliar algum do impacto dos regressos no desenvolvimento das regiões de origem, atendendo a que a quase totalidade dos regressados se dirige para a mesma região de onde havia saído. Reconstruímos o padrão dos regressos e analisamos o perfil dos regressados com informação dos fluxos entre os anos 1980 e 2011 a partir de revisão da literatura existente; os indicadores do Eurostat permitem análise do volume mais recente das migrações de regresso. Constatamos uma relativa homogeneidade no perfil e dos regressos do passado, ao contrário da diferenciação dos regressos posteriores, resultantes de uma emigração que também se diversificou.
Abstract In this paper we analyse return migration to Portugal in a historical perspective, most based on the Portuguese scientific literature produced on the subject, particularly since the 1980s. With this works available, it is possible to reconstruct the pattern of returns through its volume recorded in the censuses (or in other ways), to know returnees' profiles and to evaluate some of the return impact on the development of the regions of origin, given that almost all returnees go to the same region from which they left. We reconstructed the pattern of returns and the profile of returnees according to the information of flows between the 1980s and 2011 from the existing literature review; Eurostat indicators allow the analysis of more recent return migration volume. We verify a relative homogeneity in the profile of the returns from the past, in contrast to the differentiation of the subsequent returns, which result from an out-migration that has also diversified.
Portugal e Espanha, países para regressar Pinho, Filipa; Marques, José Carlos; Góis, Pedro
Cidades, comunidades e território (Em linha),
06/2022, Letnik:
44
Journal Article
Recenzirano
Odprti dostop
É evidente, internacionalmente, a escassez de teorias políticas focadas na emigração, comparando com a literatura sobre integração imigrante nas sociedades recetoras. Com a perspetiva transnacional, ...quando se notou que os emigrantes mantinham ligações com os seus países de origem, começou a expandir-se a análise à forma como o Estado poderia influenciar vínculos entre emigrantes e os seus países de origem e, mesmo, estimular regressos. No entanto, as políticas de vinculação e/ou de promoção de regresso de emigrantes, e respetivo estudo, tiveram início em países de emigração situados fora da Europa. Deste modo, este artigo pretende contribuir para o debate sobre políticas públicas de regresso de emigrantes e, assim, aumentar o acervo de trabalhos sobre porquê e com que objetivos estas políticas são definidas no espaço intraeuropeu, e a partir do país de origem – Portugal e Espanha.Em Portugal, cerca de duas décadas após um domínio da imigração, a emigração recuperou protagonismo e intensificou-se com o crescimento do desemprego e as medidas de austeridade, a partir de 2011. Na retoma do ciclo de crescimento positivo, o regresso destes “novos” emigrantes portugueses entrou nas agendas académica e política, com o Programa Regressar, em 2019, com medidas para recuperar emigrantes em idade ativa que tivessem saído antes de 2016. Espanha partilha com Portugal um desenvolvimento similar do seu padrão migratório, com o aumento da emigração. Em 2019, lançou um programa de política com o objetivo de recuperar emigrantes, o Un país para volver. Neste artigo fazemos a análise de conteúdo de categorias presentes nas narrativas de política, em perspetiva comparada, a partir dos enunciados destes dois programas criados para estimular o regresso de emigrantes.
The scientific production dedicated to the study of Portuguese emigration, whether in Portugal or abroad, continues to predominantly consider those who left the country as “emigrants,” and not as ...“migrants.” Despite the change that has taken place since the late 1980s with the sociologist Abdelmalek Sayad (1999a, 1999b), who saw the absolute need to reestablish the integrity of the emigrant/immigrant by reconciling these two apparently different figures into one, the Portuguese. Those who left continue to be referred to today as “emigrants.”
RuvBL1 (RuvB-like 1) and its homolog RuvBL2 are evolutionarily highly conserved AAA+ ATPases essential for many cellular activities. They play an important role in chromatin remodeling, ...transcriptional regulation and DNA damage repair. RuvBL1 and RuvBL2 are overexpressed in different types of cancer and interact with major oncogenic factors, such as β-catenin and c-Myc regulating their function. We solved the first three-dimensional crystal structure of the human RuvBL complex with a truncated domain II and show that this complex is competent for helicase activity. The structure reveals a dodecamer consisting of two heterohexameric rings with alternating RuvBL1 and RuvBL2 monomers bound to ADP/ATP, that interact with each other via the retained part of domain II. The dodecameric quaternary structure of the R1ΔDII/R2ΔDII complex observed in the crystal structure was confirmed by small-angle X-ray scattering analysis.
Interestingly, truncation of domain II led to a substantial increase in ATP consumption of RuvBL1, RuvBL2 and their complex. In addition, we present evidence that DNA unwinding of the human RuvBL proteins can be auto-inhibited by domain II, which is not present in the homologous bacterial helicase RuvB. Our data give new insights into the molecular arrangement of RuvBL1 and RuvBL2 and strongly suggest that in vivo activities of these highly interesting therapeutic drug targets are regulated by cofactors inducing conformational changes via domain II in order to modulate the enzyme complex into its active state.
Eosinophilic gastrointestinal diseases (EGID) are a group of conditions characterized by histopathologic eosinophilic infiltrates in one or more segments of the gastrointestinal (GI) tract. It occurs ...in the absence of known causes for eosinophilia. It can affect every part of the gastrointestinal tract, but eosinophilic ascites (EA) is uncommon. There is a clinical overlap between EGID and GI involvement of hypereosinophilic syndrome (HES), so distinguishing them may not be easy. We report a case of eosinophilic gastroenteritis in a 26-year-old-woman with the uncommon presentation of eosinophilic ascites after delivery. It is vital to maintain a high grade of suspicion to diagnose these disorders and exclude the secondary causes since treatment varies. In addition, the occurrence of this postpartum syndrome has been described, so it is essential to recognize this entity in this period.
PDF
