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A Renehan

Publications and source records attributed to A Renehan.

13 recordsLinked to original sources
PubMed2003

Both high intratumoral microvessel density determined using CD105 antibody and elevated plasma levels of CD105 in colorectal cancer patients correlate with poor prognosis.

CD105 and its ligand transforming growth factor beta (TGFbeta) are modulators of angiogenesis, which drives tumour growth and metastasis. Tumour microvessel density (MVD) has proven to be an important determinant of prognosis. In this study, we have examined the prognostic value of MVD identified using Mabs to the pan-endothelial marker CD34 and to CD105 in 111 patients with colorectal cancer. The Mab to CD105 preferentially reacts with angiogenic endothelial cells. Of the 111 patients studied, 38 were alive and 73 had died of the disease. The median MVD values counted using anti-CD34 and anti-CD105 were 5 (range 1.40-9.00) and 3.10 (range 0.90-8.00), respectively. Kaplan-Meier survival analysis revealed that only MVD values obtained using CD105 Mab correlated with survival. Patients with a high MVD, above the median (3.10), showed the worst prognosis. A similar outcome was observed when MVD was divided into quartiles. In order to ascertain if this strong expression of CD105 in the tumour vasculature is reflected in patients' plasma, circulating levels of CD105, TGFbeta1 and TGFbeta3 together with the receptor-ligand complexes were quantified in patients with colorectal carcinoma and normal controls. Results showed that except for TGFbeta1, the levels of all other molecules were significantly elevated compared with controls. The levels of CD105 were positively correlated with Dukes' stages. A lower TGFbeta1 level was noted in patients with carcinoma over the controls. Furthermore, TGFbeta3 and CD105/TGFbeta3 complexes were markedly lowered in postoperative compared with preoperative plasma samples. Immunostaining revealed that TGFbeta1 was expressed in cancer cells but TGFbeta3 in the stromal cells, whereas CD105 was exclusively expressed in vascular endothelial cells of tumour blood vessels. In conclusion, this study demonstrates that MVD quantified using a Mab to CD105 is an independent prognostic parameter for survival of patients with colorectal cancer, and that plasma levels of CD105, TGFbeta1, TGFbeta3 and CD105/TGFbeta complexes may be useful markers for assessing disease progression. These data have led us to propose that quantification of these determinants may prove useful to monitor therapeutic efficacy in patients with colorectal cancer, especially those who are being treated with antiangiogenic therapies.

Adult↗
PubMed2003

Immunodetection and molecular forms of plasma vascular endothelial growth factor-C.

Vascular endothelial growth factor (VEGF)-C is a member of the VEGF family. VEGF-C is involved in developmental lymphangiogenesis and may be important in pathological lymphangiogenesis, lymphatic invasion and metastasis in carcinoma. We describe the development of an indirect enzyme-linked immunosorbent (ELISA) assay for the quantification of VEGF-C in plasma. Capture of VEGF-C was achieved using goat anti-human VEGF-C antibody, followed by detection with rabbit anti-human VEGF-C antibody. The sensitivity of the assay was amplified using the biotin-avidin and enhanced chemiluminescence (ECL) systems. The assay was highly sensitive and reproducible with a detection range of 0.4-100 U/ml and the intra- and inter-assay variations were less than 8%. Substitutional tests demonstrated that the assay was specific for VEGF-C with no cross-reaction with VEGF-A or VEGF-D. Practical application of the assay was evaluated in 41 colorectal cancer patients and 31 controls. Median plasma levels of VEGF-C were 35.0 U/ml (range: 17.4-75.9 U/ml) in colorectal cancer patients in contrast to 11.5 U/ml (range: 5.4-21.5 U/ml) in controls (p<0.001). Moreover, VEGF-C levels tended to be elevated in patients with advanced disease compared to early disease, but this was not statistically significant owing to a relatively small number of patients in each group. Immunoprecipitation and immunoblotting confirmed detection of VEGF-C in plasma and revealed that two forms of VEGF-C were present in the plasma corresponding to approximately 40 and approximately 80 kDa. The measurement of plasma VEGF-C offers opportunities to explore clinical applications in the management of malignancy, in particular in the prediction of lymphatic spread and in other lymphangiogenesis-related diseases.

Adenocarcinoma↗
PubMed1996

Clinical significance of the tumour capsule in the treatment of parotid pleomorphic adenomas.

The propensity of pleomorphic adenomas to recur is generally attributed to the biological nature of the tumour, and surgery close to the capsule is perceived as undesirable. At the Christie Hospital, Manchester, between 1947 and 1992, 475 tumours arising within the superficial portion of the parotid gland were treated by two surgical techniques: extracapsular dissection (380 patients) and superficial parotidectomy (95). Recurrence rates were 2 per cent in each group (median follow-up 12.5 years). Contact of the tumour with the facial nerve was recorded in 51 per cent of patients. There was no difference between the treatment groups in the incidence of permanent facial nerve injury (2 versus 1 per cent respectively). This study demonstrates that dissection in close proximity to the tumour is possible without inducing recurrence and that in practice the microinvasion of the capsule by tumour buds has limited clinical significance.

Adenoma, Pleomorphic↗
PubMed1996

Long-term follow-up of over 1000 patients with salivary gland tumours treated in a single centre.

Between 1947 and 1992, 1403 patients with 1432 salivary gland tumours were treated at the Christie Hospital, Manchester. There were 1194 epithelial neoplasms: parotid, 1082 (91 per cent); submandibular, 47 (4 per cent); minor glands, 65 (5 per cent). The commonest histological diagnoses were pleomorphic adenoma (n = 776) and adenolymphoma (n = 159). A total of 244 carcinomas were seen (adenoid cystic carcinoma, n = 75). Treatment was primarily surgical, conservative where possible, and determined by tumour extent and not histology. Adjuvant radiation therapy was used in over half the definitively treated malignancies. The recurrence rate following the treatment of 551 new parotid pleomorphic adenomas was 1.6 per cent at median follow-up 12.5 (range 1-34) years, increasing to 15 per cent in the secondarily referred group (n = 170). For patients with definitively treated primary salivary carcinomas (n = 148), the disease-free survival rate at 5, 10 and 15 years was 58, 47 and 45 per cent respectively. Using multivariate analysis, clinical stage was the most important predictor of survival; the 10-year survival rate for stages I-IV was 96, 70, 47 and 19 per cent respectively.

Adenolymphoma↗
PubMed1996

An analysis of the treatment of 114 patients with recurrent pleomorphic adenomas of the parotid gland.

BACKGROUND: Nerve preserving surgery is widely recommended for recurrent parotid pleomorphic adenomas though the risk of further relapse may be high. Adjuvant radiotherapy may improve control but its exact role requires clarification. METHODS: A series of 114 patients with first recurrences treated between 1952 and 1992 is reviewed. Treatment modality was either surgery alone (SG; n = 63) or surgery with radiotherapy (SG + RT; n = 51). Results were determined with respect to long-term tumor control (K-M life-tables) and facial nerve function. RESULTS: The rate to second recurrence was 15% (17/114), median follow-up 14 years. There were no cases of malignant degeneration. Multinodular recurrences treated by SG were at particular high risk of relapse, but control was significantly improved with adjuvant radiotherapy (SG versus SG = RT; 43% versus 4% at 15 years, P = 0.008). In contrast, no difference was demonstrated in the uninodular tumor group (SG versus SG = RT; 15% versus 13% at 15 years, P = 0.9). The incidence of permanent facial nerve injury was 15%. CONCLUSIONS: This study emphasizes the distinction between multinodular and uninodular recurrences; the former is at high risk of relapse and benefits from adjuvant radiotherapy whereas solitary tumors may be adequately treated by surgery alone.

Adenoma, Pleomorphic↗
PubMed1995

Apoptosis, intrinsic radiosensitivity and prediction of radiotherapy response in cervical carcinoma.

Apoptosis is an important mechanism of cell death in tumours and it is seen both prior to and following radiotherapy. In this study patients with proven carcinoma of the cervix had measurement made of the percentage of apoptotic cells (apoptotic index or AI) in pre-therapy biopsies. Measurements of intrinsic radiosensitivity (SF2), already shown to be a predictor of outcome, had previously been made on the same pre-therapy biopsies. Mitotic index (MI) and Ki-67 antigen staining were also recorded as markers for proliferation. Patients were divided into those with an AI above or below the median and in general increasing apoptosis was associated with poor prognosis. The 5-year survival rate for tumours with an AI below the median was 79% and was significantly greater than the rate of 47% for those with an AI above the median (p = 0.003). There was also a significantly increased 5-year local recurrence-free rate for patients with an AI below the median compared with those with an AI above the median (79 versus 61%, p = 0.012). In addition, AI and SF2 acted as independent prognostic indicators. Patients with both an SF2 and AI value above the median did badly (25% 5-year survival, 46% local control) compared with those with an SF2 and AI below the median (80% 5-year survival, 100% local control). Apoptosis showed correlation with MI (n = 66, r = 0.34, p = 0.002) and cell staining for the Ki-67 antigen (n = 57, r = 0.25, p = 0.03), but neither MI nor Ki-67 were related to patient outcome. This suggests that while apoptosis may be a reflection of tumour proliferation this cannot in itself explain the ability of apoptosis to predict clinical outcome for this series of patients. The study raises the possibility of AI and SF2 being used together as predictors of tumour response to radiotherapy.

Adult↗
PubMed1993

Acute enlargement of the tongue.

Acute enlargement of the tongue can present as an emergency. The problems of management in the acute situation and the diagnosis of the underlying condition are discussed and illustrated with reference to four unusual cases. There is a case for a simple classification and such a classification is presented.

Abscess↗