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Biomedical subjects

V Save

Publications and source records attributed to V Save.

7 recordsLinked to original sources
PubMed2006

Plasma and dietary carotenoid, retinol and tocopherol levels and the risk of gastric adenocarcinomas in the European prospective investigation into cancer and nutrition.

Despite declining incidence rates, gastric cancer (GC) is a major cause of death worldwide. Its aetiology may involve dietary antioxidant micronutrients such as carotenoids and tocopherols. The objective of this study was to determine the association of plasma levels of seven common carotenoids, their total plasma concentration, retinol and alpha- and gamma-tocopherol, with the risk of gastric adenocarcinoma in a case-control study nested within the European Prospective Investigation into Cancer and Nutrition (EPIC), a large cohort involving 10 countries. A secondary objective was to determine the association of total sum of carotenoids, retinol and alpha-tocopherol on GCs by anatomical subsite (cardia/noncardia) and histological subtype (diffuse/intestinal). Analytes were measured by high-performance liquid chromatography in prediagnostic plasma from 244 GC cases and 645 controls matched by age, gender, study centre and date of blood donation. Conditional logistic regression models adjusted by body mass index, total energy intake, smoking and Helicobacter pylori infection status were used to estimate relative cancer risks. After an average 3.2 years of follow-up, a negative association with GC risk was observed in the highest vs the lowest quartiles of plasma beta-cryptoxanthin (odds ratio (OR) = 0.53, 95% confidence intervals (CI) = 0.30-0.94, P(trend) = 0.006), zeaxanthin (OR = 0.39, 95% CI = 0.22-0.69, P(trend) = 0.005), retinol (OR = 0.55, 95% CI = 0.33-0.93, P(trend) = 0.005) and lipid-unadjusted alpha-tocopherol (OR = 0.59, 95% CI = 0.37-0.94, P(trend) = 0.022). For all analytes, no heterogeneity of risk estimates or significant associations were observed by anatomical subsite. In the diffuse histological subtype, an inverse association was observed with the highest vs lowest quartile of lipid-unadjusted alpha-tocopherol (OR = 0.26, 95% CI = 0.11-0.65, P(trend) = 0.003). These results show that higher plasma concentrations of some carotenoids, retinol and alpha-tocopherol are associated with reduced risk of GC.

Adenocarcinoma↗
PubMed2005

Hepatocellular carcinoma tumour thrombus in a re-canalised para-umbilical vein: detection by 18-fluoro-2-deoxyglucose positron emission tomography imaging.

This case report describes an unusual site of tumour thrombus in a re-canalised para-umbilical vein, in a patient with hepatocellular carcinoma (HCC) and cirrhosis. The tumour thrombus was suspected on conventional radiography and confirmed using PET imaging, illustrating the complimentary value of structural and functional imaging in achieving the correct diagnosis.

Carcinoma, Hepatocellular↗
PubMed1998

Why is p53 protein stabilized in neoplasia? Some answers but many more questions?

The p53 pathway provides a physiological system for integrating signals from diverse insults and eliciting adaptive cellular responses that include (but importantly are not restricted to) growth arrest and apoptosis. Defects in the pathway are prevalent in cancer, most notably being associated with mis-sense mutations in p53 itself. This leads to the inability of p53 to act as a transcription factor and thus to the non-occurrence of downstream events. Recent data indicate that the stability (and hence level) of p53 protein in cells is regulated by its interaction with mdm2: this results in enhanced p53 degradation by ubiquitin-mediated events. Since mdm2 is itself regulated by p53, loss of function of p53 leads to lack of mdm2 and thus to p53 protein accumulation. This provides a mechanistic explanation for the observation that p53 accumulation is associated with neoplasia. It may be that accumulation of p53 in the absence of p53 mutation can occur as a consequence of mdm2 defects, as well as being a physiological response in many situations. Another recent development is the recognition of p53 homologues (p73 alpha, p73 beta, and KET) which have many sequence and probable structural features in common with p53. It seems likely that this will reveal another layer of complexity in the control and regulation of p53 and its role in physiology and pathology.

Humans↗
PubMed1998

An immunochemical analysis of mdm2 expression in human breast cancer and the identification of a growth-regulated cross-reacting species p170.

mdm2 is a 491 amino acid nuclear protein which is involved in complex interactions with important cell-cycle and stress-response regulators including p53, Rb and E2F. Recent data implicate mdm2 in the regulation of both p53 activity and level, and burgeoning data suggest that mdm2 may be involved in human epithelial tumourigenesis, including breast cancer. In this study the expression of mdm2 protein has been investigated in a series of 54 human breast carcinomas using immunoblotting methods. Overexpression of the predominant p90 mdm2 isoform is common in breast cancer (54 per cent) and this is not frequently a consequence of gene amplification. There is no relationship between p90 expression and either p53 protein expression or p53 mutational status. Additional mdm2 immunoreactive species of differing mobilities are identifiable, greatly complicating the analysis. For example, a p170 form is seen in many breast cancer samples (44 per cent) using 2A10 but is not identified by 3G5. This 2A10 immunoreactive species, which is almost certainly not an mdm2 isoform, is a growth-regulated protein, being undetectable in resting peripheral blood lymphocytes and rising to high levels after PHA stimulation. In contrast to mdm2 (p90), p170 is not induced by DNA damage caused by UV light. p170 is identifiable in mdm2 null cells by immunoblotting and is detected as a nuclear protein. While mdm2 immunostaining studies are increasing, this report highlights the complexity of mdm2 analysis in vivo and emphasizes the need to correlate immunohistological and biochemical assays since, in some mdm2 (p90) negative tumours, nuclear immunoreactivity may be identified as a consequence of cross-reacting species such as p170.

Adenocarcinoma↗
PubMed1997

APC expression in normal human tissues.

The tumour suppressor gene APC codes for a 2843-amino acid protein whose precise functions are still poorly understood. This paper describes the development of two new antisera to APC (to amino- and carboxy-terminal epitopes) which permit localization of the protein by immunohistochemistry in archival paraffin sections. The protein is expressed in a wide variety of normal epithelial tissues. Its distribution frequently coincides with the location of post-replicative cells within tissues. Staining patterns demonstrate that the APC protein, although often diffusely cytoplasmic in distribution, may also accumulate in the apical and immediately subapical regions, or along the lateral margins of certain cells. These results indicate that APC is significant in many tissues in addition to the colorectal epithelium. They are compatible with a function related to signalling at the adherens junction and possibly with other more complex roles in cells committed to terminal differentiation.

Adenomatous Polyposis Coli Protein↗
PubMed1995

Demonstration of DNA damage/repair in individual cells using in situ end labelling: association of p53 with sites of DNA damage.

We describe the development and application of in situ end labelling (ISEL) to identity sites of damaged DNA in the nuclei of individual cells. In cell culture, exposure to a variety of genotoxic agents induced a dose and time-dependent increase in nuclear labelling. In addition, examination of histological sections of human skin exposed to solar-stimulated UV light showed ISEL in both keratinocytes and superficial dermal cells, with the same spatial and temporal distribution as that of a marker of DNA repair, PCNA (proliferating cell nuclear antigen). Using co-localization techniques and confocal microscopy, we found increased levels of p53 in many ISEL-positive cells in vitro, with a similar distribution of labelling in the nucleus. This observation provides further evidence for a direct role of p53 in the recognition of damaged DNA. Thus, ISEL should prove a convenient method for demonstrating genotoxic insult in individual cells and in histological material, and may have value in toxicological screening. This high-resolution microscopy technique can also be used to compare the spatial distribution of various proteins implicated in the response to DNA damage with the sites of the lesion.

Animals↗