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1.  Potential role for peroxisome proliferator activated receptor (PPAR) in preventing colon cancer 
Gut  2003;52(9):1317-1322.
Background: Peroxisome proliferator activated receptors (PPARs) are nuclear hormone receptors involved in genetic control of many cellular processes. PPAR and PPAR have been implicated in colonic malignancy. Here we provide three lines of evidence suggesting an inhibitory role for PPAR in colorectal cancer development.
Methods: Levels of PPAR mRNA and protein in human colorectal cancers were compared with matched non-malignant mucosa using RNAse protection and western blotting. APCMin/+ mice were randomised to receive the PPAR activator methylclofenapate 25 mg/kg or vehicle for up to 16 weeks, and small and large intestinal polyps were quantified by image analysis. The effect of methylclofenapate on serum stimulated mitogenesis (thymidine incorporation), linear cell growth, and annexin V and propidium iodide staining were assessed in human colonic epithelial cells.
Results: PPAR (mRNA and protein) expression levels were significantly depressed in colorectal cancer compared with matched non-malignant tissue. Methylclofenapate reduced polyp area in the small intestine from 18.7 mm2 (median (interquartile range 11.1, 26.8)) to 9.90 (4.88, 13.21) mm2 (p=0.003) and in the colon from 9.15 (6.31, 10.5) mm2 to 3.71 (2.71, 5.99) mm2 (p=0.009). Methylclofenapate significantly reduced thymidine incorporation and linear cell growth with no effect on annexin V or propidium iodide staining.
Conclusions: PPAR may inhibit colorectal tumour progression, possibly via inhibition of proliferation, and may be an important therapeutic target.
PMCID: PMC1773786  PMID: 12912864
peroxisome proliferator activated receptor; methylclofenapate; colon cancer
2.  Specificity and sensitivity of immunocytochemistry for detecting P-glycoprotein in haematological malignancies. 
Journal of Clinical Pathology  1994;47(7):619-624.
AIMS--To determine the optimal working conditions of the alkaline phosphatase-antialkaline phosphatase (APAAP) method to establish a specific and sensitive assay for the detection of low numbers of MDR positive cells in patients with hematological malignancies. METHODS--Three monoclonal antibodies (C-219, JSB-1, MRK-16) were used for the detection of P-glycoprotein (P-gp) in cell lines and in samples from 43 patients with haematological malignancies. The results of the APAAP method were compared with western blotting for specificity and sensitivity. RESULTS--Excellent correlation was obtained between optimised APAAP and western blotting, except in the case of multiple myeloma. JSB-1 seemed to be the more useful monoclonal antibody for the APAAP which was more sensitive than western blotting in its ability to detect single P-gp positive cells. CONCLUSIONS--Methods for P-gp detection, as defined by multidrug resistant (MDR) cell lines, are not necessarily optimal and specific for clinical samples and may lead to higher false positive and negative results, according to the conditions and the monoclonal antibodies used.
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PMCID: PMC502088  PMID: 7916349
3.  Comparison of western blot analysis and immunocytochemical detection of P-glycoprotein in multidrug resistant cells. 
Journal of Clinical Pathology  1989;42(7):719-722.
A sensitive immunocytochemical technique was developed to detect a 170,000 dalton cell membrane glycoprotein (P-gp) in cell lines resistant to vincristine and vinblastine with varying degrees of resistance. P-gp was shown very clearly using the C219 monoclonal antibody and immunocytochemical detection with either antialkaline phosphate or peroxidase-antiperoxidase with silver gold intensification. There was good correlation between the results obtained with immunocytochemical detection of P-gp in single cells and Western blot analysis. The technique is easily performed and can detect P-gp in relatively small numbers of cells that Western blot analysis could miss and is suitable for clinical application.
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PMCID: PMC1142021  PMID: 2569484
6.  Chemotherapy in advanced ovarian cancer: four systematic meta-analyses of individual patient data from 37 randomized trials. Advanced Ovarian Cancer Trialists' Group. 
British Journal of Cancer  1998;78(11):1479-1487.
The purpose of this systematic study was to provide an up to date and reliable quantitative summary of the relative benefits of various types of chemotherapy (non-platinum vs platinum, single-agent vs combination and carboplatin vs cisplatin) in the treatment of advanced ovarian cancer. Also, to investigate whether well-defined patient subgroups benefit more or less from cisplatin- or carboplatin-based therapy. Meta-analyses were based on updated individual patient data from all available randomized controlled trials (published and unpublished), including 37 trials, 5667 patients and 4664 deaths. The results suggest that platinum-based chemotherapy is better than non-platinum therapy, show a trend in favour of platinum combinations over single-agent platinum, and suggest that cisplatin and carboplatin are equally effective. There is no good evidence that cisplatin is more or less effective than carboplatin in any particular subgroup of patients.
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PMCID: PMC2063202  PMID: 9836481
7.  Horizontal transmission of hepatitis B virus amongst British 2nd World War soldiers in South-East Asia. 
Postgraduate Medical Journal  1991;67(783):39-41.
Infection with hepatitis B virus (HBV) is much more common in tropical than in temperate countries. Visitors to the tropics are thus at risk from HBV, though the degree of risk, and the routes of infection involved are uncertain. We report serological markers of HBV in two groups of 2nd World War soldiers, who served in the Thai/Burma jungles. The groups comprised 100 ex-prisoners of the Japanese (POW), and 100 Burma Campaign Veterans (BCV). Surface antigen to HBV (HbsAg) was positive in 0% of POW and 2% of BCV (P = not significant). Surface antibody (anti-HBs) and core antibody (anti-HBc) were both positive in 40% POW and 13% BCV (P less than 0.001). Quoted UK prevalence rates for these markers are 0.1% for HBsAg, 1.5% for anti-HBs and 0.7% for anti-HBc. Both groups thus show very high rates of past HBV infection. For the POW there were many possible reasons, including contaminated surgical instruments and needles, blood transfusions, and multiple beatings with common weapons. None of these factors operated significantly for BCV. Malarial transmission was, however, intense in both groups, though more so in POW. The data thus again raise the possibility of horizontal transmission of HBV by biting insects in tropical countries.
PMCID: PMC2398940  PMID: 1711690
11.  Cysticercosis: a new hope. 
PMCID: PMC1443445  PMID: 6434112
12.  Persisting nutritional neuropathy amongst former war prisoners. 
Of 898 former Far East prisoners of war, assessed between 1968 and 1981, 49 (5.5%) had evidence of persisting symptomatic neurological disease dating back to their periods of malnutrition in captivity. The commonest syndromes were peripheral neuropathy (often of "burning foot" type), optic atrophy, and sensori-neural deafness. Though nutritional neuropathies disappeared soon after release in most ex-Far East prisoners of war, in some they have persisted up to 36 years since exposure to the nutritional insult.
PMCID: PMC491588  PMID: 6292369
14.  Strongyloides stercoralis infection in former Far East prisoners of war. 
British Medical Journal  1979;2(6190):572-574.
Out of 602 consecutive people who had been prisoners of war in the Far East and were screened for tropical diseases, 88 (15%) were found to have Strongyloides stercoralis infection a mean period of 30 years after their return from the tropics. The classical strongyloid creeping eruption was the most common symptom (84%), while gastrointestinal disturbances were rare (5%). Thiabendazole was highly effective in eradicating the infection. Strongyloidiasis is an important condition, as when the host is immunosuppressed fatal hyperinfection may occur. Many undiagnosed cases of strongyloidiasis must exist among former prisoners of war, and it is thus important to identify and treat these patients.
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PMCID: PMC1596511  PMID: 497706
15.  Strongyloidiasis in ex-Far East prisoners of war. 
British Medical Journal  1977;1(6067):1007.
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PMCID: PMC1605923  PMID: 851822

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