1,720,988 research outputs found
Innovation through Tradition: The Current Challenges in Cancer Treatment
Full text linkDespite the huge efforts in identifying novel risk factors, earlier diagnostic markers and alternative therapeutic approaches, malignant disorders continue to pose the second leading cause of death worldwide [...
Financing Mental Health Facilities During the Economic Recession: Evidence from the Private Finance Initiative Policy in the United Kingdom.
No full textThe economic crisis in Europe raised several complications in addressing infrastructure needs in public-based healthcare systems. In Western Europe, governments’ budget constraints, together with collateral healthcare-related issues such as ageing population, reduced the capability to develop modern and efficient infrastructure as well as technological upgrade of existing ones. Mental health facilities represent a peculiar aspect in this context, as pathologies require a unique treatment when compared to other medical services. Long-term hospitalization, day-by-day assistance, soft-approach therapies are specific features triggering the necessity of separate facilities for mental health treatment, or at least a distinct management within a general hospital. From an economic point of view, public-private partnerships (PPPs) could help decision-makers in tackling healthcare investment shortage, making the related infrastructure market appealing for private financing and management. As outlined in this commentary, the experience from the Private Finance Initiative (PFI) in the United Kingdom represents a step-stone for privately-financed mental health facilities, with over 8,000 beds generated in the last 15 years, both in separate structures and in general hospitals. An analysis of this model demonstrate some benefits in terms of availability and efficiency have been reached, but concerns remain terms of value for money and side-services delivery
Integrating Gemcitabine-Based Therapy With AdipoRon Enhances Growth Inhibition in Human PDAC Cell Lines
Full text linkPancreatic ductal adenocarcinoma (PDAC) accounts for 90% of all pancreatic cancers. Albeit its incidence does not score among the highest in cancer, PDAC prognosis is tremendously fatal. As a result of either aggressiveness or metastatic stage at diagnosis, chemotherapy constitutes the only marginally effective therapeutic approach. As gemcitabine (Gem) is still the cornerstone for PDAC management, the low response rate and the onset of resistant mechanisms claim for additional therapeutic strategies. The first synthetic orally active adiponectin receptor agonist AdipoRon (AdipoR) has recently been proposed as an anticancer agent in several tumors, including PDAC. To further address the AdipoR therapeutic potential, herein we investigated its pharmacodynamic interaction with Gem in human PDAC cell lines. Surprisingly, their simultaneous administration revealed a more effective action in contrasting PDAC cell growth and limiting clonogenic potential than single ones. Moreover, the combination AdipoR plus Gem persisted in being effective even in Gem-resistant MIA PaCa-2 cells. While a different ability in braking cell cycle progression between AdipoR and Gem supported their cooperating features in PDAC, mechanistically, PD98059-mediated p44/42 MAPK ablation hindered combination effectiveness. Taken together, our findings propose AdipoR as a suitable partner in Gem-based therapy and recognize the p44/42 MAPK pathway as potentially involved in combination outcomes
Genistein Prevents Apoptosis and Oxidative Stress Induced by Methylglyoxal in Endothelial Cells
No full textGlycolytic overload promotes accumulation of the highly reactive dicarbonyl compounds, resulting in harmful conditions called dicarbonyl stress. Methylglyoxal (MG) is a highly reactive dicarbonyl species and its accumulation plays a crucial pathophysiological role in diabetes and its vascular complications. MG cytotoxicity is mediated by reactive oxygen species (ROS) generation, a key event underlying the intracellular signaling pathways leading to inflammation and apoptosis. The identification of compounds able to inhibit ROS signaling pathways and counteract the MG-induced toxicity is a crucial step for developing new therapeutic strategies in the treatment of diabetic vascular complications. In this study, the effect of genistein, a natural soybean isoflavone, has been evaluated on MG-induced cytotoxicity in human endothelial cells. Our results show that genistein is able to counteract the MG-induced apoptosis by restraining ROS production, thus inhibiting the MAPK signaling pathways and caspase-3 activation. These findings identify a beneficial role for genistein, providing new insights for its potential clinical applications in preserving endothelial function in diabetic vascular complications
Inorganic phosphate as a novel signalling molecule with antiproliferative action in MDA-MB-231 breast cancer cells
No full textInorganic phosphate (Pi) is an essential nutrient to living organisms. It plays a key role in diverse physiological functions, including osteoblast differentiation and skeletal mineralization.
Relevantly, Pi is emerging as an important signalling molecule capable of modulating multiple cellular functions by altering signal transduction pathways, gene expression and protein abundance in many cell types.
To our knowledge, no research has been directed at determining the consequences of elevated Pi on behaviour of breast cancer cells.
In this study we investigate the effects of Pi on proliferation of MDA-MB-231 breast cancer cells.
Here we report that Pi inhibits proliferation of MDA-MB-231 cells by slowing-down cell cycle progression, without apoptosis occurrence. We found that Pi causes the cells to accumulate in G1 phase in a dose and time dependent manner. Accordingly, G1 accumulation was associated with a decrease of cyclin A and cyclin E and an increase of cell cycle inhibitors p21 and p27 protein levels, respectively. Moreover, the Pi-induced antiproliferative effect was dinamically accompanied by profound changes in ERK1/2 and STAT3 protein and phosphorylation levels in response to Pi.
Altogether, our data represent the first evidence of Pi acting as a novel signalling molecule in MDA-MB-231 breast cancer cells, capable of eliciting a strong antiproliferative action. The potential clinical significance and therapeutic applications by our data will be discussed
Forskolin sensitizes pancreatic cancer cells to gemcitabine via Stat3 and Erk1/2 inhibition
No full textCytotoxic chemotherapy, including gemcitabine-based regimens, represents the mainstay
of treatment for locally advanced and metastatic pancreatic cancer. However, the response to
chemotherapy is absolutely unsatisfactory and the prognosis of pancreatic cancer remains very poor.
Therefore, it would be greatly beneficial to develop therapeutic approaches that cause pancreatic
cancer cells to increase their sensitivity to chemotherapeutic drug gemcitabine. Forskolin is a natural
cAMP elevating agent used for centuries in traditional medicine and its safety has been also
documented in modern medicine. Notably, forskolin is emerging as a very interesting molecule to
possibly use in cancer therapy. In the present study, we investigated the effects of forskolin on the
proliferation, migration and sensitivity to gemcitabine of pancreatic cancer cells, carrying out flow
cytometry-based assays of cell-cycle progression and cell death, wound-healing and MTT assays,
direct cell number counting and immunoblotting experiments. Here, we show that forskolin exerts
significant growth and migratory inhibitory effects on Panc-1 and AsPC-1 pancreatic cancer cells. In
addition, we report that forskolin strongly enhances gemcitabine-induced antiproliferative effects by
both cell cycle inhibition and cell death induction. Importantly, the forskolin-induced potentiation of
antiproliferative effect by gemcitabine is preceded and accompanied by a strong inhibition of
phosphorylation levels of Stat3 and Erk1/2 proteins. Altogether, our data enforce the evidence of
forskolin acting as a compound with anticancer activity and provide a rationale for the design of in
vivo/clinical studies exploring forskolin as a gemcitabine sensitizer/adjuvant to possibly use in
pancreatic cancer patients
cAMP elevation down-regulates beta3 integrin and Focal Adhesion Kinase and inhibits leptin-induced migration of MDA-MB-231 breast cancer cells
No full text""Breast cancer is one of the most common malignancies and a major cause of cancer death in women throughout the world. The high mortality rate associated with breast cancer is mainly due to a propensity of the tumor to metastasize, even if small or undetectable. Given the relevant role of leptin in breast cancer growth and metastasis, novel strategies to counteract biological effects of this obesity-linked cytokine are warranted.. Recently, we demonstrated that in MDA-MB-231 breast cancer cells, intracellular cAMP elevation completely abrogates both ERK1\\\/2 and STAT3 phosphorylation in response to leptin and, very surprisingly, provided evidence that leptin, when cAMP levels are increased, drives cells towards apoptosis associated to a marked decrease of Bcl2 protein levels and accompanied by down-regulation of Protein Kinase A (PKA).. The aim of this study was to investigate the role of cAMP in leptin-associated motility of breast cancer cells. Here we show that cAMP elevation completely prevents leptin-induced migration of MDA-MB-231 breast cancer cells. Interestingly, the inhibition by cAMP elevating agents of leptin-mediated cell migration is accompanied by a strong decrease of β3 integrin subunit and Focal Adhesion Kinase (FAK) protein levels. . Analysis of the underlying cAMP-dependent molecular mechanisms revealed that PKA blockers counteract in part the inhibition by cAMP elevation of leptin-induced migration, whereas completely prevent the antiproliferative action by cAMP elevation. Moreover, a cAMP analogue which specifically activates Epac and not PKA has inhibitory effect on leptin-induced cell migration as well.. The present study confirms initial evidence for the efficacy of cAMP elevation against oncogenic effects of leptin, identifies β3 integrin subunit and FAK as proteins strongly down-regulated by cAMP elevation and suggests that both cAMP\\\/PKA- and cAMP\\\/Epac-dependent pathways are involved in inhibition of leptin-induced migration of MDA-MB-231 breast cancer cells.. The potential clinical significance and therapeutic applications by our data will be discussed.. "
Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Variations on the Author
Full text link“Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship
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