Evidence for Oxidative Pathways in the Pathogenesis of PD: Are Antioxidants Candidate Drugs to Ameliorate Disease Progression?

Parkinson's disease (PD) is a progressive neurodegenerative disorder that arises due to a complex and variable interplay between elements including age, genetic, and environmental risk factors that manifest as the loss of dopaminergic neurons. Contemporary treatments for PD do not prevent or reverse the extent of neurodegeneration that is characteristic of this disorder and accordingly, there is a strong need to develop new approaches which address the underlying disease process and provide benefit to patients with this debilitating disorder. Mitochondrial dysfunction, oxidative damage, and inflammation have been implicated as pathophysiological mechanisms underlying the selective loss of dopaminergic neurons seen in PD.

The Cyclic Nitroxide TEMPOL Ameliorates Oxidative Stress but Not Inflammation in a Cell Model of Parkinson's Disease.

The cyclic nitroxide TEMPOL exerts anti-oxidative and anti-inflammatory effects, and thus may provide therapeutic benefit in Parkinson's disease (PD), in which mitochondrial dysfunction, oxidative damage and inflammation have been implicated as pathophysiological mechanisms underlying the selective loss of dopaminergic neurons. Markers of oxidative stress and inflammation were investigated in a cell model of differentiated human neuroblastoma (SH-SY5Y) cells treated with the neurotoxin, 6-hydroxydopamine (6-OHDA). Treatment with TEMPOL ameliorated 6-OHDA-mediated cytotoxicity and attenuated biomarkers of oxidative stress including: mitochondrial superoxide anion free radical production, lipid peroxidation, induction of heme oxygenase 1 (HO-1) protein expression and NFκB activation.

Serum IgA1 shows increased levels of 2,6-linked sialic acid in breast cancer.

The lectin agglutinin (HPA) recognizes altered glycosylation in solid cancers and the identification of HPA binding partners in tumour tissue and serum is an important aim. Among the many HPA binding proteins, IgA1 has been reported to be the most abundant in liver metastases. In this study, the glycosylation of IgA1 was evaluated using serum samples from patients with breast cancer (BCa) and the utility of IgA1 glycosylation as a biomarker was assessed.

A targeted glycoproteomic approach identifies cadherin-5 as a novel biomarker of metastatic breast cancer.

Aberrant glycosylation has long been recognised as a hallmark of cancer, and is increasingly being exploited in biomarker discovery studies. Helix pomatia agglutinin (HPA) is known to bind aberrant glycans associated with metastatic breast cancer, and was used here to isolate glycoproteins from pooled breast cancer serum samples of (i) patients with recurrent breast cancer and (ii) patients with no sign of recurrence 5years after diagnosis of their primary tumour. Pregnancy zone protein, the polymeric immunoglobulin receptor and cadherin-5 emerged as potential markers of metastasis following proteomic identification of HPA binding glycoproteins.

Lectin array-based strategies for identifying metastasis-associated changes in glycosylation.

Since 2005, lectin microarray technology has emerged as a relatively simple yet powerful technique for the comprehensive analysis of glycoprotein glycosylation. Lectin microarrays represent a new analytical method that can be used to explore the human glycome, a unique source of markers of diseases including cancer. The lectin microarray technology is a sensitive tool with the potential to allow high-throughput analysis of cancer-associated changes in glycosylation.

Lectin microarray profiling of metastatic breast cancers.

Altered protein glycosylation compared with the disease-free state is a universal feature of cancer cells. It has long been established that distinct glycan structures are associated with specific forms of cancer, but far less is known about the complete array of glycans associated with certain tumors. The cancer glycome has great potential as a source of biomarkers, but progress in this field has been hindered by a lack of available techniques for the elucidation of disease-associated glycosylation.

Significant changes in dietary intake and supplement use after breast cancer diagnosis in a UK multicentre study.

The diagnosis of cancer can motivate survivors to alter their lifestyle habits. Healthcare providers need to be aware of what changes patients are likely to make in order to derive more pertinent recommendations; however, few studies have reported pre- and post-diagnostic lifestyle behaviours. Semi-quantitative food frequency questionnaires (FFQs) completed approximately 1 year after diagnosis were used to evaluate dietary intake and supplement use before and after diagnosis in a cohort of 1,560 breast cancer patients participating in the UK, prospective DietCompLyf study.

A sensitive assay to measure biomarker glycosylation demonstrates increased fucosylation of prostate specific antigen (PSA) in patients with prostate cancer compared with benign prostatic hyperplasia.

Background: Prostate specific antigen (PSA) measurement is used for the diagnosis of prostate cancer (PCa) but the test lacks specificity due to the number of false positive readings. The glycosylation of PSA is altered in PCa but studies in this area have been limited to few clinical samples and/or require advanced laboratory facilities. An assay to assess PSA glycosylation was established using equipment available in most routine biomedical testing laboratories.

Lignans and breast cancer risk in pre- and post-menopausal women: meta-analyses of observational studies.

Phyto-oestrogens are plant compounds structurally similar to oestradiol, which have been proposed to have protective effects against breast cancer. The main class of phyto-oestrogens in the Western diet is lignans. Literature reports on the effect of lignans in breast cancer risk have been conflicting.

Do phytoestrogens reduce the risk of breast cancer and breast cancer recurrence? What clinicians need to know.

Oestrogen is an important determinant of breast cancer risk. Oestrogen-mimicking plant compounds called phytoestrogens can bind to oestrogen receptors and exert weak oestrogenic effects. Despite this activity, epidemiological studies suggest that the incidence of breast cancer is lower in countries where the intake of phytoestrogens is high, implying that these compounds may reduce breast cancer risk, and possibly have an impact on survival.

High throughput quantification of phytoestrogens in human urine and serum using liquid chromatography/tandem mass spectrometry (LC-MS/MS).

Phytoestrogens are currently the subject of intense study owing to their potential protective effects against a number of complex diseases. However, in order to investigate the interactions between phytoestrogens and disease state effectively, it is necessary to have analytical methods which are sensitive, reproducible, and require low sample volumes. We report an assay for three isoflavones (daidzein, genistein, and glycitein), two metabolites of daidzein (equol and O-desmethylangolensin), three lignans (secoisolariciresinol, enterodiol, and enterolactone), and one flavanone (naringenin) in human urine and serum.

Poisoning due to raw Gyromitra esculenta (false morels) west of the Rockies.

Vomiting with abdominal pain is a common presentation in the emergency department (ED). Without a careful history, unusual causes, such as toxic ingestion, may evade diagnosis. We report a case of an Asian couple who presented to the ED with vomiting and epigastric distress.

Cancer-associated glycoforms of gelatinase B exhibit a decreased level of binding to galectin-3.

Gelatinase B (MMP-9) and galectin-3 are widely known to participate in tumor cell invasion and metastasis. Glycans derived from MMP-9 expressed in MCF-7 breast cancer and THP-1 myeloid leukemia cells were compared with those from MMP-9 expressed in natural neutrophils. The many O-linked glycans of neutrophil gelatinase B presented a cluster of mainly galactosylated core II structures, 46% of which were ligands for galectin-3; 11% contained two to three N-acetyllactosamine repeating units that are high-affinity ligands for the lectin.

Short-term phytoestrogen supplementation alters insulin-like growth factor profile but not lipid or antioxidant status.

Phytoestrogens are plant compounds that have been proposed to have a variety of health benefits. The aim of this study was to assess the effects of these compounds on a number of physiological endpoints. Subjects were given a single intake of a phytoestrogen-rich (80 mg total phytoestrogens) supplement containing soy, rye and linseed (Phase 1), followed by a week-long intervention using the same supplement (Phase 2) (80 mg total phytoestrogens daily).

Effect of red clover-derived isoflavone supplementation on insulin-like growth factor, lipid and antioxidant status in healthy female volunteers: a pilot study.

Background: Isoflavones are estrogen-like plant compounds that may protect against cardiovascular disease and endocrine-responsive cancer. Isoflavones may, because of their ability to act as selective estrogen receptor modulators, alter insulin-like growth factor (IGF) status.

Objective: The aim of this study was to assess the effect of 1-month isoflavone supplementation (86 mg/day red clover-derived isoflavones) on IGF status.

The influence of dietary lectins on the cell proliferation of human breast cancer cell lines in vitro.

Background: Lectins, carbohydrate proteins, bind non-covalently to glycoconjugate of normal and malignant cells. If used in cell culture, they can influence cellular proliferation. In this study the in vitro effects of six dietary lectins on the cell proliferation of human breast cancer cell lines were investigated.

In vitro isoflavone supplementation reduces hydrogen peroxide-induced DNA damage in sperm.

Isoflavones are plant compounds, proposed to have health benefits in a variety of human diseases, including coronary heart disease and endocrine-responsive cancers. Their physiological effects include possible antioxidant activity, therefore suggesting a role for isoflavones in the prevention of male infertility. The aim of this study was to test the antioxidant effects of the isoflavones genistein and equol on sperm DNA integrity, assessed in vitro after hydrogen peroxide-mediated damage, using the comet assay.

Proteome and glycosylation mapping identifies post-translational modifications associated with aggressive breast cancer.

Changes in glycosylation of glycoproteins and glycolipids is a common feature of cancer and may influence cancer cell behaviour, perhaps by enabling cell-cell interactions which favour metastasis or by allowing cancer cells to evade immuno-surveillance. Studies to identify glycosylation changes in human cancer have often used immunohistochemical techniques with lectins or antibodies and human tissue sections. Whilst some detailed biochemical studies have been performed there are few clinically relevant studies since the numbers of specimens evaluated are often very small.

IGF status is altered by tamoxifen in patients with breast cancer.

Aims: An increased concentration of insulin-like growth factor 1 (IGF-1) is an independent risk factor for premenopausal breast cancer. Tamoxifen is thought initially to reduce concentrations of IGF-1 and increase concentrations of the IGF binding proteins. The aim of this study was to compare concentrations of IGF-1, IGF binding protein 1 (IGF-BP1), and IGF-BP3 in patients with breast cancer (n = 14) with those seen in control subjects (n = 23) and to assess the effect of tamoxifen on IGF status in these patients.

Helix pomatia agglutinin lectin-binding oligosaccharides of aggressive breast cancer.

Predicting long-term outcome after breast-cancer diagnosis remains problematic, particularly for patients with clinically small, axillary lymph node- negative tumours. Evidence suggests that the lectin Helix pomatia agglutinin (HPA) identifies oligosaccharides associated with poor-prognosis cancer. Our aim was to identify oligosaccharides that bind HPA in aggressive breast cancers.

Effect of phytoestrogen and antioxidant supplementation on oxidative DNA damage assessed using the comet assay.

Antioxidant species may act in vivo to decrease oxidative damage to DNA, protein and lipids thus reducing the risk of coronary heart disease and cancer. Phytoestrogens are plant compounds which are a major component of traditional Asian diets and which may be protective against certain hormone-dependent cancers (breast and prostate) and against coronary heart disease. They may also be able to function as antioxidants, scavenging potentially harmful free radicals.

Expression of N-acetyl galactosaminylated and sialylated glycans by metastases arising from primary breast cancer.

This study examines the Helix pomatia lectin (HPA) binding characteristics of metastases arising from primary breast cancer, and compares HPA binding patterns with binding of Dolichos biflorus lectin (DBA), Limax flavus lectin (LFA), and a monoclonal antibody against the Tn epitope. Of 81 blocks of metastases in a range of tissues, taken at autopsy from 46 individuals, 79% were HPA positive. No site specificity with regard to HPA binding was observed.

Release and analysis of polypeptides and glycopolypeptides from formalin-fixed, paraffin wax-embedded tissue.

Archival tissue specimens are commonly stored as formalin-fixed, paraffin wax-embedded blocks. Formalin fixation facilitates excellent morphological preservation, and the immunoreactivity of many antigens is preserved, but formalin-induced chemical cross-linking of proteins renders them insoluble and inaccessible to standard biochemical extraction and analytical methods. Thus, biochemical analysis of tissue components identified by histochemistry, with the advantage of long-term clinical follow-up, is precluded.