Detection of candidate biomarkers of prostate cancer progression in serum: a depletion-free 3D LC/MS quantitative proteomics pilot study.

BACKGROUND: Prostate cancer (PCa) is the most common male cancer in the United Kingdom and we aimed to identify clinically relevant biomarkers corresponding to stage progression of the disease. METHODS: We used enhanced proteomic profiling of PCa progression using iTRAQ 3D LC mass spectrometry on high-quality serum samples to identify biomarkers of PCa. RESULTS: We identified >1000 proteins. Following specific inclusion/exclusion criteria we targeted seven proteins of which two were validated by ELISA and six potentially interacted forming an 'interactome' with only a single protein linking each marker. This network also includes accepted cancer markers, such as TNF, STAT3, NF-κB and IL6. CONCLUSIONS: Our linked and interrelated biomarker network highlights the potential utility of six of our seven markers as a panel for diagnosing PCa and, critically, in determining the stage of the disease. Our validation analysis of the MS-identified proteins found that SAA alongside KLK3 may improve categorisation of PCa than by KLK3 alone, and that TSR1, although not significant in this model, might also be a clinically relevant biomarker.

Are you also what your mother eats? Distinct proteomic portrait as a result of maternal high-fat diet in the cerebral cortex of the adult mouse.

Epidemiological studies suggest an association between maternal obesity and adverse neurodevelopmental outcomes in offspring. Our aim was to compare the global proteomic portrait in the cerebral cortex between mice born to mothers on a high-fat or control diet who themselves were fed a high-fat or control diet. Male mice born to dams fed a control (C) or high-fat (H) diet 4 weeks before conception and during gestation, and lactation were assigned to either C or H diet at weaning. Mice were killed at 19 weeks and their cerebral cortices were analysed using a two-dimensional liquid chromatography-mass spectrometry methodology. In total, 6 695 proteins were identified (q<0.01), 10% of which were modulated in at least one of the groups relative to controls. In silico analysis revealed that mice clustered based on the diet of the mother and not their own diet and that maternal high-fat diet was significantly associated with response to hypoxia/oxidative stress and apoptosis in the cerebral cortex of the adult offspring. Maternal high-fat diet resulted in distinct endophenotypic changes of the adult offspring cerebral cortex independent of its current diet. The identified proteins could represent novel therapeutic targets for the prevention of neuropathological features resulting from maternal obesity.

The inter-regional epidemiological study of childhood cancer (IRESCC): case-control study of children with central nervous system tumours.

Tumours of the central nervous system comprise 23% of all childhood cancers and form the most common group of solid malignancies. Little is know about their aetiology. The present report concerns the results of a case-control study of 78 incident cases of central nervous system tumours in children. No case-control differences were detected for the following: pre-natal diagnostic X-rays, general anaesthetics during pregnancy, pregnancy infections, pregnancy drugs (including sedatives, tranquillizers and anti-convulsants), alcohol consumption in pregnancy, child's birthweight, breast-feeding, childhood illnesses, previous medication in the child. A significant excess of case mothers had suffered from diseases of the nervous system (RR 2.6). There was a deficit of children who had been immunised among the case children which approached significance, and an excess of congenital abnormalities among cases which also approached significance. There was a small excess of neoplastic disease among case parents. The results of this study suggest that in our patients genetic rather than environmental factors are more important, but the small numbers included in the present study meant that no definite conclusions could be reached.

The Inter-Regional Epidemiological Study of Childhood Cancer (IRESCC): case control study of children with bone and soft tissue sarcomas.

The Inter-Regional Epidemiological Study of Childhood Cancer included 43 cases of soft tissue and 30 cases of bone sarcomas, together with their 146 matched controls. Analysis of a wide range of aetiological factors revealed few risk factors relating to events during the index pregnancy, the earlier medical experiences of the case child, or parental medical, occupational and smoking history. Associations which did emerge included: lower birth weight in children with Ewing's tumour, an excess of mothers of children with soft tissue sarcoma with symptoms of toxaemia in pregnancy; and more children with rhabdomyosarcoma who received antibiotics soon after birth. There was some evidence that mothers of children with soft tissue sarcoma may have had reduced fertility with a significant excess of the case mothers having no other pregnancies. Slight excesses of congenital malformations in the case children and of malignant and benign/borderline neoplastic disease in the older mothers were consistent with the existence of a degree of genetic predisposition in the development of the tumours in this series.

The Inter-Regional Epidemiological Study of Childhood Cancer (IRESCC): past medical history in children with cancer.

The Inter-Regional Epidemiological Study of Childhood Cancer (IRESCC) collected interview and medical information relating to the child's past medical experiences from parents of 555 children diagnosed with cancer and parents of 1110 unaffected matched controls. No significant associations emerged overall for ante-natal care, place and mode of delivery, length of gestation, birth weight, condition at birth, special care, neonatal procedures or breast-feeding. Few risk factors relating to previous illnesses and medication were found, although increasing numbers of illnesses appeared to be associated with an increased risk of childhood cancer, particularly acute lymphoblastic leukaemia. A highly significant excess of case children had not been immunised (p = 0.005). In general, these results indicate that past medical experiences have little influence on the development of cancer in children.

The Inter-Regional, Epidemiological Study of Childhood Cancer (IRESCC): case-control study in children with germ cell tumours.

In 1980-1983 members of IRESCC interviewed parents of 555 children with newly diagnosed cancer on topics of possible aetiological significance. Identical questions were asked of the parents of 1100 control children chosen from hospital admissions and general practitioner lists. Medical information was confirmed whenever possible by cross-checking with NHS records. Data for the 41 children with germ cell tumours and their 82 controls are reported here. The cases had more major congenital malformations than controls, including one neural tube defect. More case than control mothers and fathers reported occupational exposure to chemicals. Nine close relatives of cases had multiple primary tumours, which were often benign or of low-grade malignancy, compared with 1 hospital control and 3 general practitioner control relatives. Cases and controls differed with respect to birth weight and paternal age. No case-control differences were shown for: birth rank, maternal age, chronic illnesses and smoking, mothers' reproductive histories and oral contraceptive usage. In index pregnancies there were no case-control differences for maternal illness, infections, alcohol intake and X-ray and ultrasound exposure. There was no difference between cases and controls for the frequency of twinning the families.

The Inter-Regional Epidemiological Study of Childhood Cancer (IRESCO). Study design, control selection and data collection.

The Inter-Regional Epidemiological Study of Childhood Cancer (IRESCC) was established to investigate the role of possible aetiological factors in childhood cancer, with particular emphasis on environmental exposures to the foetus and family history of certain diseases including cancer. Incident cases occurring in three Health Service regions (the West Midlands, Yorkshire and North Western) were matched for age and sex with two sets of control children. A total of 555 cases and 1110 controls were entered into the study. The parents of each index child were interviewed with respect to events during the relevant pregnancy, occupation, smoking habits, and past medical history of themselves, the child's siblings and other relatives. Ninety-three per cent of case parents approached agreed to be interviewed, and approximately 90% of controls were ranked first or second on the control selection lists. After the interview information was verified by reference to antenatal and other medical records. Obstetric and general practitioner records were abstracted for approximately 90% of cases and controls. Information derived from the interview and that from medical records was coded separately. The data collected by each region have been pooled and case-control comparisons of potential aetiological factors will be carried out, using matched triplet analyses.

Inter-Regional Epidemiological Study of Childhood Cancer (IRESCC): childhood cancer and the consumption of debendox and related drugs in pregnancy.

Attention has recently focused on the possible teratogenic effects of the combination antiemetic doxylamine succinate, dicyclomine hydrochloride and pyridoxine hydrochloride (Debendox/Bendectin) prescribed to pregnant women. The Inter-Regional Epidemiological Study of Childhood Cancer (IRESCC), a case-control investigation has analysed data derived from interview reports and medical records of 555 mothers of children (under 15 years) with cancer and 1110 mothers of matched control children. Separate analyses of interview reports and medical records both suggested that antiemetic ingestion during the index pregnancy does not increase the risk of developing childhood malignant disease in the exposed foetus. No dose-response relationship was evident. The lack of any significant relative risks held good for diagnostic sub-groups and when the trimester of ingestion was considered. Our results suggest that antimetics of this type are unlikely to be transplacental carcinogens.

Ultrasound examinations in pregnancy and childhood cancer.

Analysis of information obtained in an inter-regional epidemiological study by interviewing the parents of 555 children with malignancy diagnosed between 1980 to 1983 and the parents of 1110 control children did not reveal any significant association between exposure to ultrasound examination in pregnancy and risk of childhood cancer.