Lactoferrin and cancer disease prevention

Lactoferrin (LF) is an iron-binding glycoprotein that is composed of the transferrin family and is predominantly found in the products of the exocrine glands located in the gateways of the digestive, respiratory, and reproductive systems, suggesting a role in the non-specific defence against invading pathogens. Additionally, several physiological roles have been attributed to LF, namely regulation of iron homeostasis, host defence against infection and inflammation, regulation of cellular growth, and differentiation and protection against cancer development and metastasis. These findings have suggested LF's great potential therapeutic use in cancer disease prevention and/or treatment, namely as a chemopreventive agent. This review looks at the recent advances in understanding the mechanisms underlying the multifunctional roles of LF and future perspectives on its potential therapeutic applications.Fundação para a Ciência e a Tecnologia (FCT) - SFRH/BPD/26064/2005

The role of osteopontin in tumour progression and metastasis in breast cancer

The use of cancer biomarkers to anticipate the outlines of disease has been an emerging issue, especially as cancer treatment has made such positive steps in the last few years. Progress in the development of consistent malignancy markers is imminent because advances in genomics and bioinformatics have allowed the examination of immense amounts of data. Osteopontin is a phosphorylated glycoprotein secreted by activated macrophages, leukocytes, and activated T lymphocytes, and is present in extracellular fluids, at sites of inflammation, and in the extracellular matrix of mineralized tissues. Several physiologic roles have been attributed to osteopontin, i.e., in inflammation and immune function, in mineralized tissues, in vascular tissue, and in kidney. Osteopontin interacts with a variety of cell surface receptors, including several integrins and CD44. Binding of osteopontin to these cell surface receptors stimulates cell adhesion, migration, and specific signaling functions. Overexpression of osteopontin has been found in a variety of cancers, including breast cancer, lung cancer, colorectal cancer, stomach cancer, ovarian cancer, and melanoma. Moreover, osteopontin is present in elevated levels in the blood and plasma of some patients with metastatic cancers. Therefore, suppression of the action of osteopontin may confer significant therapeutic activity, and several strategies for bringing about this suppression have been identified. This review looks at the recent advances in understanding the possible mechanisms by which osteopontin may contribute functionally to malignancy, particularly in breast cancer. Furthermore, the measurement of osteopontin in the blood or tumors of patients with cancer, as a way of providing valuable prognostic information, will be discussed based on emerging clinical data.Fundação para a Ciência e a Tecnologia (FC

Lymph node tissue kallikrein-related peptidase 6 mRNA: a progression marker for colorectal cancer

BACKGROUND: A most important characteristic feature for poor prognosis in colorectal cancer (CRC) is the presence of lymph node metastasis. Determination of carcinoembryonic antigen (CEA) mRNA levels in lymph nodes has proven powerful for quantification of disseminated tumour cells. Here, we investigate the utility of human tissue kallikrein-related peptidase 6 (KLK6) mRNA as a progression biomarker to complement CEA mRNA, for improved selection of patients in need of adjuvant therapy and intensified follow-up after surgery. METHODS: Lymph nodes of pTNM stage I-IV CRC-(166 patients/503 lymph nodes) and control (23/108) patients were collected at surgery and analysed by quantitative RT-PCR. RESULTS: Lymph node KLK6 positivity was an indicator of poor outcome (hazard ratio 3.7). Risk of recurrence and cancer death increased with KLK6 lymph node levels. Patients with KLK6 lymph node levels above the 90th percentile had a hazard ratio of 6.5 and 76 months shorter average survival time compared to patients with KLK6 negative nodes. The KLK6 positivity in lymph nodes with few tumour cells, that is, low CEA mRNA levels, also indicated poor prognosis (hazard ratio 2.8). CONCLUSION: In CRC patients, lymph node KLK6 positivity indicated presence of aggressive tumour cells associated with poor prognosis and high risk of tumour recurrence. British Journal of Cancer (2012) 107, 150-157. doi: 10.1038/bjc.2012.220 www.bjcancer.com Published online 14 June 2012 (C) 2012 Cancer Research U

Significance of osteopontin expression in human invasive breast tumour stroma

Osteopontin has been reported to stimulate cell adhesion, migration and specific signalling functions. Its overexpression has been found in melanoma, breast, lung, colorectal, stomach and ovarian cancer. However, its overexpression and role in human breast cancer remains to be elucidated. In this study, invasive breast tumours from 129 patients were examined by immunohistochemistry in order to assess osteopontin association with several molecular tumour markers. Additionally, its relationship with proliferation and angiogenesis was determined. Ultimately, other tumour variables such as histological grade, tumour size and nodal status were also assessed. Results achieved showed that no statistical significant association exists between osteopontin expression and major clinicopathological parameters or angiogenesis, except for the number of lymph nodes involved. However, a correlation with some molecular markers was observed, namely with P-Cadherin, EGFR, cytokeratin 14 and vimentin. Additionally, higher proliferation rates were found for the tumours expressing osteopontin. Although several studies refer osteopontin as a potential breast cancer biomarker, it is still not clear if it can provide important diagnosis information, evaluate treatment effects or assess the potential for metastatic disease in patients.Fundação para a Ciência e a Tecnologia (FCT

The Socio-economic Impact of Social Computing: Proceedings of a Validation and Policy Options Workshop

This report presents the major outcomes of a validation and policy options workshop on social computing, held at IPTS in Seville, on 26-27 February 2008. It points to a number of relevant issues (including methodological and conceptual ones) that need to be taken into account in a study of the socio-economic impacts of social computing. It argues that there is little room for direct policy interventions in social computing but that framework conditions and impacts at sector-level (e.g. education, government) need to be considered. The report also discusses the future of social computing and the opportunities it offers Europe.JRC.J.4-Information Societ

A longitudinal study of perceived health during pregnancy: antecedents and outcomes

Perceived health was studied longitudinally in a sample of 364 nulliparous women. Psychosocial, contextual, and biomedical factors were taken into account to predict medically relevant versus benign symptoms which were then used to predict perceived health over time. The results of structural equation modeling showed that pregnancy adjustment and medically relevant symptoms which were affected by social support, perceived stress, and negative affect predicted later perceived health. The outcomes of perceived health were examined during the third trimester in terms of medical care utilization and emergency room visits. Perceived health solely accounted for medical care utilization, while emergency room visits were accounted by medical care utilization and perceived stress