Focal Adhesions And Focal Complexes

Integrin-dependent cell adhesion, spreading and migration on a substrate requires the dynamic formation and dissolution of sites of contact between the cell and the substrate. In vitro, these integrin rich sites of attachment are classified as belonging to one of two main types. When they are small and associated with the leading edge of an advancing cell membrane or when they are present at the end of filopodia they are referred to as focal complexes or point contacts (51, 52). When they are...

Sarcomas

Leiomyoma and lieosarcomas are capable of metastatic spread, and equally distributed throughout the small intestine. The tumours comprise relative circumscribed whorls of smooth muscle that lack a proper capsule with variable degrees of hyalinization. As the smooth muscle enlarges, they tend to expand the serosal aspect of the intestine and may stretch and even ulcerate the mucosa. Sarcomata of the oesophagus are rare. Most are limited to single case reports. Leiomyosarcoma and rhabdomyosarcoma...

Conclusion And Perspectives

HGF exhibits biological activities responsible for dynamic tissue remodeling during embryogenesis and tissue regeneration. HGF and Met are involved in organogenesis and repair, mediating epithelial-mesenchymal (or -stromal) or other heterotypic cell-cell interactions. The motogenic activity of HGF is potent and clearly a wide variety of tumour cells utilize the HGF-Met system during acquisition of invasive and metastatic potentials. Tumour-stromal interactions, as mediated by the HGF-Met system...

Diagnostic Confirmation of Metastatic MTC

In patients with MTC, calcitonin provides a unique tumour marker and levels should be monitored regularly following total thyroidectomy. In a report of 123 patients with MTC treated by total thyroidectomy, postoperative calcitonin levels were low or non-detectable when MTC was confined to the thyroid gland (67 ). In contrast only 8 ofpatients had low calcitonin levels when extrathyroidal spread was present (57). Further reports suggest that calcitonin levels rarely return to zero following...

Malignant Phaeochromocytoma

The incidence of phaeochromocytoma is approximately 1-2 cases per 100,000 population. Malignant phaeochromo-cytomas accounts for only 10 of all phaeochromocytomas but in extra-adrenal tumours, located along the course of the sympathetic chain the incidence of malignancy rises to 40-50 (116). There is a higher incidence of extra-adrenal tumours in children compared with adults. Tumours are usually cystic with areas of haemorrhage and necrosis. Vascular invasion is a histological feature of...

Detection of Soluble Fragments

Detection of the soluble fragments produced by ectodomain shedding in the serum of patients has been used as a marker for disease. Soluble L-selectin is found at high concentrations (1.5-2.0 in normal human serum. Levels are decreased in inflammatory diseases like rheumatoid arthritis, vasculitis and in adult respiratory distress syndrome. This may reflect reduced shedding or strong binding of the soluble fragment to cell surface ligands or both (270). Higher serum levels of soluble L-selectin...

Genetic instability

Cellular genetic instability is important in determining the susceptibility to carcinogenic events and once transformation has occurred in determining the biological behaviour of the tumour. Cells become more susceptible to such genetic events with aging which has been related to the activity of the enzyme telomerase which controls the length of the chromosomal telomere (131) and may be relevant to genetic instability which is a feature of maligant cells. Shortening of the cell telomere length...

Conclusion

It is likely that metastasis will remain the leading cause of treatment failure and death from gynaecological cancer for the forseeable future. Key to immediate improvement in outcome is to ensure that patients receive optimum conventional management from site specialist multi-disciplinary teams working on Calman-Hine principles. Such treatment being 1. Guidance on commissioning Cancer services. Improving outcomes in Gynaecological Cancers - (1999) NHS executive . 2. Nguyen NH, Averette...

Tumour residuum after surgery

The size of residual tumour remaining after surgical cytoreduction for advanced ovarian cancer may reflect tumour biology i.e. its degree invasiveness of abdominal structures as well as the degree of surgical effort. It is the second most important prognostic factor after stage. There is an inverse ratio between the size of residual tumour and patient outcome and in a small meta-analysis of 4 randomised trials of platinum based chemotherapy, residual tumour size was the major determinant of...

Cytokines And Anticytokines

The role of cytokines in the invasion and metastasis has been controversial. This is partly due to their diverse range of biological functions depending on the cell type, cytokine type, receptor type etc. Those promoting invasion and metastasis include IL-6, HGF SF (ref 93 and Chapter 6). Strategies using cytokine to combat invasion and metastasis or to reverse those promoting cytokines have been explored. IL-4 has been shown to markedly reduce lung metastasis of renal carcinoma and extend...

Follicular Thyroid Cancer

This does not tend to occur as frequently as in papillary cancer. Tumours tend to be isolated, encapsulated (90 ) and unilateral. Total or near thyroidectomy is advocated to facilitate 13'I screening for metastatic disease and increase the efficacy of therapeutic 131I. An exception to total or near total thyroidectomy may be made in minimally invasive follicular where total thyroid lobectomy and isthmusectomy are regarded as sufficient surgical treatment. Extrathyroidal invasion in follicular...

Carcinomas

Perineal Resection

The incidence of oesophageal cancer, ranges from 5 per 100 000 in the USA to 100 per 100 000 in China. Almost 2 decades ago, 90 of oesophageal tumours were squamous cell carcinoma and 10 were adenocarcinoma. Since then, there has been a steady increase in the incidence of adenocarcinoma of the oesophagus, with some reports suggesting that adenocarcinoma now accounts for more than 50 of oesophageal tumours. It is commonest at the narrowing of the oesophagus especially at the arch of aorta, level...

Introduction

Tumour biology and mechanism of metastasis The basic molecular mechanisms employed by the invasive and metastatic cells are similar among the various types of carcinoma. Hence, the ability of tumour cells to disseminate from the primary tumour mass and to spread via blood vessels or the lymphatic system is governed by similar factors in differing tumours. The extracellular matrix (ECM) forms a barrier to the progression of tumour cells and its various constituent molecules impede this cellular...

Management Of Metastatic Anaplastic Thyroid Cancer

Locally invasive with early lymphatic and distant metastatic spread, management of metastatic disease in this uniformly fatal condition is particularly difficult. Diagnosis can usually be obtained by FNAC. Incisional biopsy should be avoided as this can result in metastatic tumour in the incision (46). Surgery should be reserved only to relieve airway obstruction or in certain instances to debulk tumours (47). Tracheostomy may be necessary to relieve airway obstruction. Tumours invade quickly...

Inhibition of Extracellular Matrix ECM Degradation

The hallmark of a malignant tumour is the ability of cancer cells to invade the basement membrane and subsequently blood vessels and the lymphatics. The basement membrane consists of collagen IV, laminin, fibronectin, elastin, heparan-sulfate proteoglycans and sometime collagen V. The invasion of these structures may be the results of a mechanical force and enzymatic degradation of the structure. The latter is primarily involved in the release of an array of matrix proteolytic enzyme. The ECM...

Mala Dolo Naggle Da

In recent years, great strides have been made in our understanding of metastasis as it relates to prostate cancer. This can only improve our clinical management of early, organ-confined disease, as we increasingly understand the biological determinants of significant as opposed to latent disease. More problematic will be the effective treatment of established metastatic disease, but several avenues of exploration have been discussed here. Effective anti-angiogenic agents, modulators of hormone...

ZO1 and the MAGUK protein family

The first protein identified in the tight junctions is ZO-1, zonular occluden-1. The protein was identified as a phosphoprotein of 210-225 kDa in size (3,4). The protein is a peripheral membrane protein enriched at the points of tight junctions. It was found to be phosphorylated on serine residues in quiescent conditions, becoming phosphorylated on tyrosine residues under stimulation. The protein is located in polarised epithelial and endothelial cells, in tight junctions, in the undercoat of...

Conclusions

Macromolecular HA inhibits angiogenesis in both in vitro and in many in vivo models, but OHA stimulates angiogenesis in these same systems. In vitro studies suggest that both interact with endothelial cell CD44H activating (OHA), or inhibiting (HA), the formation of the NFkB and AP-1 transcription factors. Examination of adult and foetal wound healing models indicate that high-molecular-weight HA is inhibitory to new blood vessel formation and that its degradation is a necessary prerequisite to...

Cancer And Cancer Metastasisrelated Genes

Key words Oncogenes, Metastasis, B-catenin, nm-23, MTA1, CD44 Abstract Neoplastic disease follows the acquisition of mutations within genes, a process that may span many years. When these mutations occur in proto-oncogenes that normally encode for proteins which control the cell cycle, DNA repair and transcriptional events, the result is deregulation of cellular proliferation and other intracellular pathways, ultimately leading to tumour development. The metastatic spread of tumours is the...

Biological Aspects

The causes of prostate cancer are unknown. Dietary, genetic, and other environmental factors are all likely to play a part (27), but their relative contributions are unclear, and they are likely to interact in a highly complex manner. The problem of latent prostate cancer, discussed in the previous section, highlights the need to understand the natural history of the disease in terms of the biological factors that influence proliferation, invasion, and metastasis. Indeed, a complete...

Clinical studies on patients with cancer

Patients with the following tumours have been tested using fatty acids Local delivery of GLA (intra-cerebral) in 15 patients with malignant gliomas resulted in regression when evaluated by computerised tomography and increased survival of the patients by 1.5-2 years (119). Patients with cerebral astrocytoma showed improvement in general condition as well as tumour (120). As already discussed, there have been significant interests and controversies in the effects of PUFAs on breast cancer. A...

Malcolm Adams And Barat Jasani

Velindre NHS Health Care Trust, Whitchurch, Cardiff CF14 2TL, The United Kingdom Bracke, Marc. Laboratory of Experimental Cancerology, University Hospital of Gent, UZG, B-9000 Ghent, Belgium Bruyneel, Erik. Laboratory of Experimental Cancerology, University Hospital of Gent, UZG, B-9000 Ghent, Belgium Carey, P. D. Surgical Unit, Belfast City Hospital, Lisburn Road, Belfast, BT9 7AB, The United Kingdom Clarke, Dayalan. University Department of Surgery, University of Wales...

Mechanisms Of Lymphomagenesis

Unlike the acute myeloid leukaemias where a number of well defined aetiological factors have emerged (benzene and other toxins, irradiation), the known causative agents of the lymphomas are largely associated with infection. The Herpes viruses (especially EBV and HHV8) are associated with the development of lymphomas and this has been well documented in groups of heavily immunosuppressed individuals such as recipients of bone marrow or solid organ transplants or patients infected with HIV....

Integrin Ligation Activates Signalling Pathways

A variety of intracellular signals are generated as integrins cluster (reviewed in (62, 63) including changes in intracellular calcium and pH, turnover of inositol phospholipids, activation of the serine threonine kinase protein kinase C and phosphorylation and dephos-phorylation on tyrosine of many molecules. As integrins do not possess any intrinsic enzyme activity they must recruit non-receptor tyrosine kinases and phosphatases which mediate integrin adhesion-dependent enzymatic events....

Tight Junction Its Possible Role In Cancer Invasion And Metastasis

Interaction and subsequent penetration of the endothelium by cancer cells is a key step in the formation of distant metastasis 46,47 . Once entering the blood circulation, tumour cells will face attack from the immune system. The surviving tumour cells travel in the circulation to distant tissues organs. Once arriving at the target organ, tumour cells will undergo a series of biochemical interactions with endothelial cells. The early interactions are likely to be mediated by...