STAT-1 expression is regulated by IGFBP-3 in malignant glioma cells and is a strong predictor of poor survival in patients with glioblastoma Laboratory investigation

Object. Insulin-like growth factor binding proteins (IGEBPs) have been implicated in the pathogenesis of glioma. In a previous study the authors demonstrated that IGFBP-3 is a novel glioblastoma biomarker associated with poor survival. Since signal transducer and activator of transcription 1 (STAT-1) has been shown to be regulated by IGFBP-3 during chondrogenesis and is a prosurvival and radioresistant molecule in different tumors, the aim in the present study was to explore the functional significance of IGFBP-3 in malignant glioma cells, to determine if STAT-1 is indeed regulated by IGFBP-3, and to study the potential of STAT-1 as a biomarker in glioblastoma. Methods. The functional significance of IGFBP-3 was investigated using the short hairpin (sh)RNA gene knockdown approach on U251MG cells. STAT-1 regulation by IGFBP-3 was tested on U251MG and U87MG cells by shRNA gene knockdown and exogenous treatment with recombinant IGFBP-3 protein. Subsequently, the expression of STAT-1 was analyzed with real-time reverse transcription polymerase chain reaction (RT-PCR) and immunohistochemistry (IHC) in glioblastoma and control brain tissues. Survival analyses were done on a uniformly treated prospective cohort of adults with newly diagnosed glioblastoma (136 patients) using Kaplan-Meier and Cox regression models. Results. IGFBP-3 knockdown significantly impaired proliferation, motility, migration, and invasive capacity of U251MG cells in vitro (p < 0.005). Exogenous overexpression of IGFBP-3 in U251MG and U87MG cells demonstrated STAT-1 regulation. The mean transcript levels (by real-time RT-PCR) and the mean labeling index of STAT-1 (by IHC) were significantly higher in glioblastoma than in control brain tissues (p = 0.0239 and p < 0.001, respectively). Multivariate survival analysis revealed that STAT-1 protein expression (HR 1.015, p = 0.033, 95% CI 1.001-1.029) along with patient age (HR 1.025, p = 0.005, 95% CI 1.008-1.042) were significant predictors of shorter survival in patients with glioblastoma. Conclusions. IGFBP-3 influences tumor cell proliferation, migration, and invasion and regulates STAT-1 expression in malignant glioma cells. STAT-1 is overexpressed in human glioblastoma tissues and emerges as a novel prognostic biomarker.

Coordinate Hyperactivation of Notch1 and Ras/MAPK Pathways Correlates with Poor Patient Survival: Novel Therapeutic Strategy for Aggressive Breast Cancers

Aberrant activation of Notch and Ras pathways has been detected in breast cancers. A synergy between these two pathways has also been shown in breast cell transformation in culture. Yet, the clinical relevance of Notch-Ras cooperation in breast cancer progression remains unexplored. In this study, we show that coordinate hyperactivation of Notch1 and Ras/MAPK pathways in breast cancer patient specimens, as assessed by IHC for cleaved Notch1 and pErk1/2, respectively, correlated with early relapse to vital organs and poor overall survival. Interestingly, majority of such Notch1 (high)Erk(high) cases encompassed the highly aggressive triple-negative breast cancers (TNBC), and were enriched in stem cell markers. We further show that combinatorial inhibition of Notch1 and Ras/MAPK pathways, using a novel mAb against Notch1 and a MEK inhibitor, respectively, led to a significant reduction in proliferation and survival of breast cancer cells compared with individual inhibition. Combined inhibition also abrogated sphere-forming potential, and depleted the putative cancer stem-like cell subpopulation. Most importantly, combinatorial inhibition of Notch1 and Ras/MAPK pathways completely blocked tumor growth in a panel of breast cancer xenografts, including the TNBCs. Thus, our study identifies coordinate hyperactivation of Notch1 and Ras/MAPK pathways as novel biomarkers for poor breast cancer outcome. Furthermore, based on our preclinical data, we propose combinatorial targeting of these two pathways as a treatment strategy for highly aggressive breast cancers, particularly the TNBCs that currently lack any targeted therapeutic module. (C) 2014 AACR.

Reseña bibliográfica : poor economics. A radical rethinking of the way to fight global poverty

El libro recientemente publicado Poor Economics -y la técnica de evaluaciones aleatorias que dan sustento a sus conclusionestienen el potencial para cambiar radicalmente la manera de diseñar políticas para combatir la pobreza en el mundo. El libro fue escrito por Abhijit Banerjee y Esther Duflo, dos jóvenes reconocidos economistas del MIT (Massachusetts Institute of Technology). Duflo, nacida en Francia y educada en el École Normale Supérieure de Paris y MIT, fue ganadora en 2010 del premio John Bates Clark al mejor economista menor de 40 años y considerada por la revista Foreign Policy como una de los 100 intelectuales más influyentes del mundo. Abhijit Banerjee educado en la Universidad de Calcuta (su ciudad de origen) y la Universidad de Harvard también es ganador de numerosos premios.

An analysis of poverty and aquatic resources use - focusing especially on the livelihoods of the poor - in Cambodia

The main objectives of this report, which is based on the current literature and key informant interviews, is to assess and analyse the nature and distribution of poverty and aquatic resources use, focusing especially on the livelihoods of the poor. It describes and reports different ways of measuring poverty that are used in Cambodia and quantifies the diverse nature and geographic distribution of aquatic resources use in Cambodia. (PDF contains 55 pages)

Synthesis report with pro-poor trade research findings and policy recommandations

The purpose of the project was to investigate international trade in fisheries products and its relationship to poverty alleviation and livelihoods of poor aquatic resource users in developing countries in Asia, and to identify options to improve the effectiveness of poverty reduction through international seafood trade. The project directly addressed the EC-PREP priority area of trade and development, and indirectly provided valuable insight to two other priority areas: food security and sustainable rural development; and institutional capacity building. [PDF contains 60 pages.]

Marine ornamentals trade in the Philippines and options for its poor stakeholders

The objective of this project in the Philippines is to promote the development of policy changes and other actions related to the trade in ornamental fish with Europe which support poor people’s livelihoods. [PDF contains 118 pages.]

Poverty and aquatic resources in Vietnam: an assessment of the role and potential of aquatic resource management in poor people's livelihoods

This report seeks to discuss a variety of approaches to poverty in order to illustrate the diversity of poor people, and the range of ways in which people are poor, facilitating a broader understanding of poverty and the significance of aquatic resources in poor people’s livelihoods. This is intended to provide a balance to the general neglect of the poor in the pursuit of aquaculture development within the Fisheries sector. It is also intended that this approach to poverty will assist in the planning and targeting of aquatic resource interventions that aim to promote poverty alleviation. In its many different forms, poverty remains a persistent problem with a great number of people facing deprivation and vulnerable livelihoods. Rates of poverty alleviation also differ; whereas the Red River Delta has achieved the greatest reductions in poverty, the Mekong Delta has achieved the smallest improvements, with possible indications that inequality has increased (see 2.4). Inequality between regions persists despite progress in all regions. (PDF has 37 pages.)

Livelihood analysis and development of a planning support for the poor in aquaculture and aquatic resource management. Workshop proceedings. 13-15 February 2001, Thai Nguyen, Vietnam

The workshop was organized to understand and describe the livelihoods of poor people who manage aquatic resources for planning support. The purpose was to support field workers to carry out livelihood analysis and how to use this information. (PDF contains 13 pages)

The STREAM Initiative: support to regional aquatic resources management. Promoting participation, communication, and policies that support the livelihoods of poor aquatic resource users in the Asia-Pacific. Memorandum

Throughout the Asia-Pacific region capture fisheries and certain less intensive forms of aquaculture can and do play a vital role in livelihoods management, food security, and health and nutrition. Knowledge and experience exist that could be more effectively used in policy for poverty alleviation. (PDF contains 89 pages)

Some remarks on asymmetrical cultural transfer. (The Case of Slovenian Literature for Italian Readers)

Eterio Pajares, Raquel Merino y José Miguel Santamaría (eds.)

Framework for a pro-poor regional strategy on sustainable aquatic resources management in Asia-Pacific: a statement of understanding and recommendations

This statement was prepared by the participants of the FAO/NACA-STREAM Workshop on Aquatic Resources and Livelihoods: Connecting Policy and People, 17-19 March 2005, in Los Baños, Laguna, Philippines. This was the concluding event of the FAO Technical Cooperation Program (TCP) project entitled “Assistance in Poverty Alleviation through Improved Aquatic Resources Management in Asia-Pacific.” The purpose of the workshop was to review and share experiences of the NACA-STREAM Initiative, build consensus on the value of livelihoods approaches in aquatic resources management and poverty alleviation, and identify ways of promoting livelihoods approaches throughout the region. (Pdf contains 2 pages).

Aquatic resources management for sustainable livelihoods of poor people: proceedings of the DFID-ARM e-mail conference, June 2000

This e-mail conference has been organised by the DFID Aquatic Resources Management (ARM) Programme, S E Asia. It forms part of a wider process of consultation including links with other donors, with government and non-government partners and participatory livelihood assessments with vulnerable groups who benefit from aquatic resources. The objective is to provide a forum for professionals who have been involved in aquatic resources management in the context of poor peoples’ livelihoods, to share experiences, reflect on approaches and contribute to their development. Participants can submit poster presentations (2-pagers) and contribute to the discussions (via the conference website) organised around 5 key issues, set out in this discussion paper. After 4 weeks online the contributed posters and discussions will be edited into a document assessing approaches to aquatic resources management, which benefit livelihoods of poor people. This will be downloadable from the website. (PDF contains 134 pages)

Investigation into the factors associated with poor water quality in intensively cultured prawn ponds

Water quality problems are reported to be the factor limiting prawn production in the local prawn farm. This investigation was carried out to monitor water quality and its relationship to physical, chemical and biological conditions in the ponds in order to establish what factors should be monitored in order to predict problems. Pond collapse was found to be associated with high concentrations of ammonium, high pH and blue-green algae dominated phytoplankton populations. There was no easy means of predicting the imminent collapse of ponds as the phenomenon was never associated with the extreme of any of the conditions monitored. Rather it seemed to be related to the stability of the pond's algal population, which was largely unaccounted for. Recommendations toward improving water quality are proposed.

Use of SARIMA models to assess data-poor fisheries: a case study with a sciaenid fishery off Portugal

Research on assessment and monitoring methods has primarily focused on fisheries with long multivariate data sets. Less research exists on methods applicable to data-poor fisheries with univariate data sets with a small sample size. In this study, we examine the capabilities of seasonal autoregressive integrated moving average (SARIMA) models to fit, forecast, and monitor the landings of such data-poor fisheries. We use a European fishery on meagre (Sciaenidae: Argyrosomus regius), where only a short time series of landings was available to model (n=60 months), as our case-study. We show that despite the limited sample size, a SARIMA model could be found that adequately fitted and forecasted the time series of meagre landings (12-month forecasts; mean error: 3.5 tons (t); annual absolute percentage error: 15.4%). We derive model-based prediction intervals and show how they can be used to detect problematic situations in the fishery. Our results indicate that over the course of one year the meagre landings remained within the prediction limits of the model and therefore indicated no need for urgent management intervention. We discuss the information that SARIMA model structure conveys on the meagre lifecycle and fishery, the methodological requirements of SARIMA forecasting of data-poor fisheries landings, and the capabilities SARIMA models present within current efforts to monitor the world’s data-poorest resources.