Can magnetic-resonance imaging help elucidate natural history of breast cancer multicentricity?
Explore the source record for details and available documents.
Breast↗
Biomedical subjects
I Taylor
Publications and source records attributed to I Taylor.
Endothelin-1 and tumour development.
There has been a growing conviction amongst oncologists that cancer is a disease characterized by changes in specific molecules. These changes include alteration in the structure, regulation or quantity of growth factors and their receptors, signal transducers and the proteins encoded by dominant or suppressor/recessive oncogenes. The role of endothelin (vasoactive peptide) in tumour cell signal transduction and mitogenesis and induction of endothelial cell growth and angiogenesis in tumour growth is discussed in this article.
Endothelin-1↗
The significance of involved tumour bed biopsy following wide local excision of breast cancer.
AIM: Following wide local excision of breast cancer approximately 25% of patients have residual disease in the tumour bed. The aim of this study was to determine whether positive bed biopsy correlated with either local recurrence or overall survival. METHOD: Following wide excision bed biopsies were taken at four separate sites from the tumour bed. Histopathological assessment of the bed biopsies was made and compared to features within the primary tumour. Patients were followed-up over a median period of 6.17 years and local recurrence and survival data documented. RESULTS: Two hundred and sixty-eight patients were included in the study and 63 had positive bed biopsies. In all, 85 patients had a recurrence of breast cancer and 69 died. Kaplan-Meier plots showed no evidence of a difference in survival between bed biopsy positive and negative patients. Bed biopsy positive patients were at greater risk of local recurrence. CONCLUSIONS: These findings suggest that positive bed biopsy is associated with an increase in local recurrence rates but has no effect on overall survival following wide excision of breast cancer.
Adult↗
Treatment of colorectal cancer in patients aged over 75.
Colorectal cancer is a common malignancy which is occurring with increasing incidence in the elderly. As the age of the population increases so the importance of this malignancy will gradually increase. In addition a high proportion of elderly patients present with intestinal obstruction secondary to colorectal cancer and therefore the management of intestinal obstruction in the elderly becomes an important surgical consideration. This review discusses the management of colorectal cancer in patients over the age of 75 in both the elective and emergency situations with particular reference to screening, surgical management and the use of adjuvant therapy.
Age Factors↗
Breast cancer imaging--what are the optimal modalities?
Explore the source record for details and available documents.
Breast Neoplasms↗
Crystal structure of the anti-fungal target N-myristoyl transferase.
N-myristoyl transferase (NMT) catalyzes the transfer of the fatty acid myristate from myristoyl-CoA to the N-terminal glycine of substrate proteins, and is found only in eukaryotic cells. The enzyme in this study is the 451 amino acid protein produced by Candida albicans, a yeast responsible for the majority of systemic infections in immuno-compromised humans. NMT activity is essential for vegetative growth, and the structure was determined in order to assist in the discovery of a selective inhibitor of NMT which could be developed as an anti-fungal drug. NMT has no sequence homology with other protein sequences and has a novel alpha/beta fold which shows internal two-fold symmetry, which may be a result of gene duplication. On one face of the protein there is a long, curved, relatively uncharged groove, at the center of which is a deep pocket. The pocket floor is negatively charged due to the vicinity of the C-terminal carboxylate and a nearby conserved glutamic acid residue, which separates the pocket from a cavity. These observations, considered alongside the positions of residues whose mutation affects substrate binding and activity, suggest that the groove and pocket are the sites of substrate binding and the floor of the pocket is the catalytic center.
Acyl Coenzyme A↗
Raised endothelin 1 levels in patients with colorectal liver metastases.
BACKGROUND: Endothelin 1 (ET-1), a vasoconstrictor peptide, has been implicated as a tumour growth stimulator and an angiogenesis factor. METHODS: To assess the involvement of ET-1 in colorectal cancer, immunoelectron microscopy for ET-1 was performed in colorectal liver metastases and normal liver (n = 6). ET-1 plasma levels were measured by radioimmunoassay in patients with colorectal cancer, with (n = 18) and without (n = 12) liver metastases, and in controls (n = 22). RESULTS: In normal liver, ET-1 was present in endothelial cells; in tumour, it was observed in endothelial cells, tumour cells and myofibroblasts. Mean(s.d.) plasma ET-1 levels were 2.75 (1.37) pg/ml in controls, 4.53(1.61) pg/ml in patients with colorectal liver metastases (P = 0.001) and 3.92(1.32) pg/ml in patients without metastases (P = 0.02). CONCLUSION: ET-1 was present in various cell types within colorectal liver metastases and raised levels were found in the plasma of patients with colorectal cancer. ET-1 may not only modulate tumour vascular tone but also act on tumour growth and angiogenesis, both locally and systemically.
Aged↗
Calmanization of general surgery.
Explore the source record for details and available documents.
Education, Medical, Graduate↗
Iodine-131-MIBG therapy of a patient with carcinoid liver metastases.
UNLABELLED: Iodine-13I-metaiodobenzylguanidine (MIBG) is highly concentrated by >60% of carcinoid metastases and thus provides a therapeutic opportunity. METHODS: A symptomatic patient with carcinoid liver metastases, unresponsive to chemotherapy combined with interferon-alpha, was subsequently treated with 131I-MIBG. RESULTS: Radionuclide therapy, which was without significant side effects, resulted in symptomatic improvement and reduced urinary 5-hydroxyindoleacetic acid levels. No new metastases were observed for 15 mo after 131I-MIBG therapy. Gross cystic change occurred in existing liver metastases, presumably as a result of ischemic necrosis. Surgical deroofing and aspiration of cysts led to regeneration of normal liver tissue. CONCLUSION: Iodine-131-MIBG therapy can provide prolonged symptomatic relief and improved quality of life in patients with metastatic carcinoid disease unresponsive to other therapies. The antitumor effect of 131I-MIBG was accompanied by few side effects, suggesting that this therapy should be considered in symptomatic patients with an early stage of disease.
3-Iodobenzylguanidine↗
Surgery for cancer.
Explore the source record for details and available documents.
Combined Modality Therapy↗
Blood vessels in liver metastases from both sarcoma and carcinoma lack perivascular innervation and smooth muscle cells.
Hepatic arterial infusion (HAI) chemotherapy as treatment for human colorectal liver metastases is promising, but not entirely satisfactory. Improved drug delivery during HAI may be achieved by manipulating the different control mechanisms of normal versus tumour blood vessels. The peptidergic/aminergic innervation of vessels in normal liver and in two animal models of liver metastasis (Lister Hooded rat with syngeneic MC28 sarcoma; athymic (nude) rat with human HT29 carcinoma) was investigated to assess the suitability of these models for future pharmacological studies. Normal liver and metastases were studied immunohistochemically for the presence of protein gene product 9.5 (PGP), neuropeptide Y (NPY), tyrosine hydroxylase (TH), calcitonin gene-related peptide (CGRP), vasoactive intestinal polypeptide (VIP) and substance P (SP). Perivascular innervation was also examined by transmission electron microscopy. In Lister rat normal livers, perivascular immunoreactive nerve fibres containing PGP, NPY, TH, CGRP and SP were observed around the interlobular blood vessels near the hilum and in the portal tracts. The highest density was seen for PGP, followed in decreasing order, by NPY, TH, CGRP and SP. VIP-immunoreactive nerves were absent. No immunoreactive nerves were observed in the hepatic lobule. In athymic rat livers, the pattern of innervation was similar, except that SP immunoreactivity was more sparse. No perivascular immunoreactive nerves were observed in either MC28 or HT29 tumours. Electron microscopy confirmed the absence of perivascular nerves. Smooth muscle cells were not observed in tumour blood vessel walls. These results are comparable with previous observations on human liver metastases and suggest that the animal models may be suitable for pharmacological studies on vascular manipulation of HAI chemotherapy.
Animals↗
Breast cancer management: is volume related to quality? Clinical Advisory Panel.
A method of carrying out region-wide audit for breast cancer was developed by collaboration between the cancer registry, providers and purchasers as part of work to fulfill the 'Calman-Hine' recommendations. In order to test the audit method, a retrospective audit in North Thames East compared practice in 1992 against current guidelines. The analysis compared care in specialist and non-specialist centres. A stratified random sample comprising 28% of all breast cancer patients diagnosed in 1992 was selected from the population-based Thames Cancer Registry. The data for 309 patients with stage I-III tumours were analysed by hospital type using local guidelines. No difference between specialist (high volume) and non-specialist centres was detected for factors important in survival. Pathological staging was good with over 70% reporting tumour size and grade. A small number of patients were undertreated; after conservative surgery, 10% (19) of women did not receive radiotherapy, and 15% (8) of node-positive premenopausal women did not receive chemotherapy or ovarian ablation. In contrast, a significant trend with hospital volume was found for several quality of life factors. These included access to a specialist breast surgeon and specialist breast nurses, availability of fine-needle aspiration (FNA), which ranged from 84% in high-volume to 42% in low-volume centres, and quality of surgery (axillary clearance rates ranged from 51% to 8% and sampling of less than three nodes from 3% to 25% for high- and very low-volume centres respectively). Confidential feedback of results to surgeons was welcomed and initiated change. The summary information gave purchasers information relevant to the evaluation of cancer services. While the audit applied present standards to past practice, it provided the impetus for prospective audit of current practice (now being implemented in North Thames).
Breast Neoplasms↗
A phase II study of regional 2-weekly 5-fluorouracil infusion with intravenous folinic acid in the treatment of colorectal liver metastases.
Forty patients with unresectable colorectal metastases confined to the liver were evaluated in a phase II study. 5-Fluorouracil (5-FU) was delivered via a surgically placed hepatic artery catheter. Patients received folinic acid (200 mg m-2) intravenously over 2 h followed by a loading dose of intra-arterial 5-FU (400 mg m-2) over 15 min, then 5-FU (1600 mg m-2) by intra-arterial infusion over the following 22 h. This was repeated on day 2 and the whole schedule was repeated every 2 weeks. Response was assessed after six treatments. The median follow-up was 17 months. Overall response rate was 46% with 8% complete response. Estimated median survival is 19 months. Site of progression was the liver alone in 55%, liver and lung in another 16% and 29% in other sites. Eight patients experienced grade 3 or 4 toxicity. The response rate of this regimen compares favourably with reported trials of intra-arterial FUDR, and our schedule is currently being compared with a similar schedule of intravenous 5-FU and folinic acid in a randomized Medical Research Council trial (CR05).
Adult↗
Increase in immunoreactivity for endothelin-1 in blood vessels of rat liver metastases: experimental sarcoma and carcinoma.
Using electron immunocytochemistry, blood vessels in the normal rat liver and in 2 different animal models of liver metastases: (1) Hooded Lister rat with MC28 tumour, a sarcoma, and (2) nude rat with HT29 tumour, a carcinoma, were investigated for the presence of endothelin-1. In the normal livers, small subpopulations of vascular endothelial cells displayed discrete immunoreactivity for endothelin-1. In the livers with malignant tumours, there was a substantial increase in endothelin-1-immunoreactive endothelial cells in vessels located at the tumour periphery. In the controls, antibody to endothelin-1 also labelled sporadically some fibroblast/fibroblast-like cells associated with the blood vessels. In contrast, intense immunoreactivity for endothelin-1 was frequently associated with the tumour cells and/or fibroblast cells in both types of tumour examined.
Animals↗
Education in pain management.
Explore the source record for details and available documents.
Anesthesiology↗
Superior mesenteric artery syndrome.
Superior mesenteric artery syndrome is a rare and controversial form of upper intestinal obstruction in which the third part of the duodenum is compressed by the overlying superior mesenteric artery. Any disease process decreasing the angle between the superior mesenteric artery and the abdominal aorta can result in the external compression of the duodenum and subsequent intestinal obstruction. The aetiology, presentation, investigation and management of this unusual condition are discussed.
Humans↗
Toward a functional analysis of private verbal self-regulation.
We developed a methodology, derived from the theoretical literatures on rule-governed behavior and private events, to experimentally investigate the relationship between covert verbal self-regulation and nonverbal behavior. The methodology was designed to assess whether (a) nonverbal behavior was under the control of covert rules and (b) verbal reports of these rules were functionally equivalent to the covert rules that control non-verbal behavior. The research was conducted in the context of teaching shopping skills to persons with mild intellectual disabilities using a self-instruction training format. In Phase 1, 4 participants were successfully taught to perform shopping skills using overt and covert self-instructions. The self-instructions were then blocked under overt and covert self-instruction conditions, which resulted in a reversal of shopping skills to baseline levels. This indicated that the overt and covert self-instructions might be controlling responding. In Phase 2, we demonstrated that the self-instructions, when used as external directives, produced successful shopping with 3 other participants. By demonstrating that self-rules can produce correct responding when used as external directives, we were more confident that it was the self-instructions and not other verbal or nonverbal behavior that controlled responding under overt, covert, and blocking conditions in Phase 1.
Adult↗