PubMed Health⌕ Search

Biomedical subjects

Elaine Kay

Publications and source records attributed to Elaine Kay.

27 records · Page 2Linked to original sources
PubMed2003

Infiltrating immune cells, but not tumour cells, express FasL in non-small cell lung cancer: No association with prognosis identified in 3-year follow-up.

Non-small cell lung cancer (NSCLC) remains a difficult disease to treat and independent prognostic markers other than tumour stage and histology have not emerged. The immune cell content of solid tumours has been associated with tumour regression and at times, tumour progression. The involvement of immune cells in prognosis of NSCLC is poorly described. Poor immune responses within solid tumours have been linked with tumour production of immunosuppressive cytokines. Tumour expression of FasL is thought to disarm responses through the transduction of a death signal in Fas-expressing T cells. The existence of the 'tumour counterattack' in vivo has been questioned. We undertook to measure T cell and macrophage infiltration of the tumour bed in NSCLC and report the association between immune cell content and prognosis in a limited, 3-year analysis of survival (n = 113). In addition we investigated FasL expression (n = 45). T cells and macrophages were found to frequently infiltrate lung tumours, albeit in small numbers. Generally there were more T cells infiltrating than macrophages. T cell and macrophage numbers were not associated with prognosis. Lung tumours were found not to express FasL, although occasional immune cells surrounding tumour cells were strongly positive. FasL expression was not associated with prognosis in this series. Thus, immune cells infiltrating NSCLC are not capable of suppressing tumour growth, nor are they associated with tumour progression. We report that lung tumours do not express the FasL, and that although some immune cells are FasL positive, this is not a reflection of general immune cell activation.

Adenocarcinoma↗
PubMed2003

Idiopathic cholangiopathy in a biliary cast syndrome necessitating liver transplantation following head trauma.

The development of total biliary casts is very unusual, especially in patients who have not undergone liver transplantation. The aetiology of these casts is uncertain but several factors are believed to play a role, including periods of fasting, haemolysis, cholangitis and recent surgery. Resultant bile stasis and/or gallbladder hypocontractility promote sludge and subsequent stone formation. Here we present the case of a previously well 66-year-old woman who developed a total biliary cast several weeks after being involved in a road traffic accident during which she sustained head injuries but no obvious liver insult. This cast was removed at laparotomy but the patient had resultant diffuse biliary tree abnormalities and persistent cholestasis and subsequently required a liver transplant. The possible aetiologies of biliary cast formation and subsequently cholangiopathy necessitating transplantation in this patient are described.

Accidents, Traffic↗
PubMed2003

The problem with KIT: clinical implications and practical difficulties with CD117 immunostaining.

Immunohistochemical staining for KIT (CD117) was performed on 144 cases of soft tissue sarcoma and 11 cases of gastrointestinal stromal tumor (GIST). Diffuse global staining in almost all neoplastic cells was a consistent feature of GIST but was also seen in some types of soft tissue sarcoma that resemble GISTs morphologically, such as synovial sarcoma and leiomyosarcoma. This finding is of diagnostic importance because some of these sarcoma types may involve the intestinal wall and simulate primary GIST. Most other positive cases showed focal staining. Although focal positivity may not be a problem in resected specimens, it has the potential to be misleading in biopsy material. Our results are concordant with some reports of CD117 expression in soft tissue tumors, but they differ from those reported by other laboratories. This discrepancy in the literature may be the result of variation in antibodies used or variation in immunohistochemical staining protocol. Regardless of the technical or scientific explanation, an understanding of the difficulties with KIT immunostaining is critical. Not only is KIT positivity used as a prerequisite for the diagnosis of GISTs, but treatment eligibility for STI571 in patients with GIST, and increasingly with other tumors, relies on positive KIT immunostaining.

Gastrointestinal Neoplasms↗
PubMed2003

Adenomatous polyposis coli gene, beta-catenin, and E-cadherin expression in proximal and distal gastric cancers and precursor lesions: an immunohistochemical study using tissue microarrays.

The aims of this study were (1) to compare protein expression of adenomatous polyposis coli (APC) gene, beta-catenin, and E-cadherin between proximal and distal gastric adenocarcinomas and (2) to investigate their use as markers of cancer risk in intestinal metaplasia (IM). The epidemiology of proximal (cardia and gastroesophageal junction) and distal (antrum and corpus) gastric carcinomas is strikingly different despite similar morphologies. Carcinoma of the distal stomach is decreasing in incidence, whereas proximal carcinomas are increasing in incidence more than any other cancer in the Western world. This phenomenon has so far not been satisfactorily explained. IM is a well-established precursor for adenocarcinoma in the distal stomach but less so in the proximal stomach. However, its specificity as a predictor of gastric carcinoma is very low. Abnormalities of APC, beta-catenin, and E-cadherin are implicated in carcinogenesis of the stomach and may show aberrant expression at early stages of the neoplastic process. This study evaluated their immunoprofiles in 3 groups: biopsies showing normal mucosa (n = 108), biopsies showing IM (n = 99), and gastric cancer resections (n = 117). In the last group, carcinoma and noninvolved mucosa were studied. All groups included material from both proximal and distal locations. The results of this study showed that there were no differences between proximal and distal locations with regard to APC, beta-catenin, or E-cadherin expression. In both locations, high normal expression rates for all 3 molecules were present in biopsies showing normal gastric mucosa or IM and noninvolved mucosa from gastric cancer resections. In carcinomas, there was a significant decrease in both APC and E-cadherin expression, whereas beta-catenin showed abnormal cytoplasmic and nuclear staining. Diffuse-type cancers showed significantly lower E-cadherin expression than intestinal types. Noninvolved mucosa from cancer resections showed normal APC, beta-catenin, and E-cadherin expression regardless of adjacent tumor type and whether the mucosa was morphologically normal or showed IM. In conclusion, proximal and distal gastric carcinomas show no differences in expression of APC, beta-catenin, or E-cadherin; thus, the observed abnormalities do not seem to contribute to the observed epidemiologic differences between these tumors. Because loss of APC, decreased E-cadherin, or abnormal beta-catenin expression did not occur in IM, even when associated with carcinoma these immunostains are unlikely to be of value in the assessment of malignant potential in IM.

Adult↗
PubMed2003

CD44v6: a potential marker of malignant transformation in intestinal metaplasia of the stomach? An immunohistochemical study using tissue microarrays.

OBJECTIVE: Intestinal metaplasia is a well-established risk factor in the development of stomach cancer. However, since the specificity is low it would be of great practical value to find a marker to separate cases of intestinal metaplasia into low and high risk for progression to dysplasia/carcinoma. So far this has not been achieved. CD44 is a cell surface molecule involved in cell-cell and cell-matrix interactions, and the spliced variant 6 has been shown to play a role in the progression of gastric carcinoma. The aim of this study was therefore to evaluate CD44v6 as a marker of increased cancer risk in intestinal metaplasia. METHODS: The current study investigated immunohistochemical CD44v6 expression in biopsies of normal gastric mucosa (n = 154) and gastric mucosa with intestinal metaplasia (n = 127). A third group consisted of cancer gastrectomies (n = 117) in which both tumour and uninvolved mucosa was studied. Proximal (cardia) and distal (corpus/antrum) locations were noted in all cases. RESULTS: There was a significant sequential increase in CD44v6 expression from normal mucosa and mucosa showing intestinal metaplasia to uninvolved mucosa adjacent to cancers without and with intestinal metaplasia to tumour. The most striking increase was from 'normal' to intestinal metaplastic mucosa adjacent to cancers. There were no differences between proximal and distal cases in any group. CONCLUSION: These findings strongly suggest that CD44v6 expression is a late phenomenon in the transformation of intestinal metaplasia to dysplasia/cancer. It may therefore be a useful marker of cancer risk in patients with intestinal metaplasia.

Adult↗
PubMed2002

Thermal preconditioning prevents peritendinous adhesions and inflammation.

Adhesion formation is one of the foremost obstacles to a reliably good outcome in tendon and joint surgery. Thermal preconditioning has been found to reduce the inflammatory response through the induction of molecular chaperone expression, a recently described family of cytoprotective intracellular proteins. The authors analyzed the effect of thermal preconditioning on the inflammatory response to surgery, on tendon healing, and on the formation of peritendinous adhesions in 16 New Zealand White rabbits. Very significant decreases in adhesion formation and in the gliding and dimensions of tendons in animals that had thermal preconditioning were found. Tendons from these animals also showed a decreased level of adhesion formation and a significantly diminished inflammatory response on histologic examination with no biomechanically significant deleterious effect on the strength of tendon healing on testing load to failure. These findings are consistent with induction of heat shock proteins by hyperthermic pretreatment. Such prevention of peritendinous adhesions and the inflammatory response to injury and surgery without compromising healing are findings that have significant implications for tendon surgery and all surgery involving joints and soft tissues.

Animals↗
PubMed2002

Lack of association between hepatitis C viral RNA in serum and liver and histologic gradings: a study on Irish anti-D-treated patients.

In this study the authors applied a reverse transcription-polymerase chain reaction (RT-PCR) assay to detect hepatitis C virus (HCV) RNA in 15 frozen liver biopsy samples from anti-D-treated patients. They also correlated the presence or absence of HCV RNA in the serum and liver of each patient with their histologic gradings. RNA was extracted from 36 frozen liver biopsy samples. These included 15 liver biopsy samples from patients infected with HCV through contamination of anti-D blood products. Three of these 15 anti-D-treated patients were receiving alpha-interferon treatment at the time of liver biopsy. Nine frozen liver biopsy samples from patients with a history of intravenous drug abuse were included as positive controls. HCV-negative frozen liver biopsy samples from 12 noninfected patients were used as negative controls. RNA was also extracted from six frozen skin biopsy specimens to check for cross-contamination of samples. Eleven of 15 anti-D-treated patients were HCV RNA positive by RT-PCR, with 100% correlation between HCV RNA in the serum and liver. The nine frozen liver biopsy samples from the intravenous drug abuse patients (positive controls) were also RT-PCR positive for HCV RNA. The 12 noninfected samples and the negative control biopsy samples were negative for HCV. Twenty-seven percent of the recombinant immunoblot assay-positive patients were serum and liver HCV RNA negative. HCV-positive patients receiving alpha-interferon therapy at the time of biopsy had cleared the virus from the serum and the liver. There was no correlation between the presence or absence of serum and liver HCV RNA with the histologic grading. This lack of correlation shows clearly the importance of histopathologic evaluation of liver biopsy samples in monitoring HCV-associated liver disease progression. In addition, this finding indicates that one cannot rely only on the presence or absence of HCV RNA in either serum or liver tissue as a parameter in monitoring HCV-associated liver disease progression in this unique cohort of anti-D-treated patients.

Blotting, Southern↗
PubMedDate not supplied

Analysis of p16 expression and allelic imbalance / loss of heterozygosity of 9p21 in cutaneous squamous cell carcinomas.

Deletions of the short arm of chromosome 9 have been reported in different types of malignancies. This chromosomal region contains a number of known tumour suppressor genes, including the p16INK4A (CDKN2A), p15INK4B and MTAP tumour suppressor genes located at 9p21. In this study twenty-two paraffin embedded invasive cutaneous SCC were examined for allelic imbalance/ loss of heterozygosity (AI/LOH) of the 9p region (in particular 9p21), and for p16 protein expression. DNA was isolated from microdissected sections of normal and tumour cells and analysed for AI/LOH by using six fluorescently labelled microsatellite markers that map to the 9p region. P16 protein expression was examined by immunohistochemistry. At each of the six microsatellite markers the majority of SCC analysed showed AI/LOH. Overall both AI/LOH within the CDKN2A locus and absence of p16 protein expression were frequent among the cutaneous SCC analysed, suggesting that p16 inactivation may play a role in cutaneous SCC development. The majority of the SCC analysed also had AI/LOH of the marker within the MTAP gene, and at markers flanking the CDKN2A gene; thus further investigation as to a possible role for these genes in the development of cutaneous SCC is warranted.

Allelic Imbalance↗