Clinical and laboratory studies in hepatocellular carcinoma

Dunk, Arthur Albert (1987) Clinical and laboratory studies in hepatocellular carcinoma. MD thesis, University of Glasgow.

Abstract

This work examines a variety of clinical and experimental aspects of hepatocellular carcinoma (HCC), both in patients with this disease and in an animal model of the condition. Most of the studies examine areas of therapeutic interest. Chapter 1. The clinical, prognostic, aetiological and pathological features of a series of 50 British HCC patients are detailed. Most patients presented in poor clinical condition and with non-specific symptoms. Cirrhosis was present in 78% and approximately 40% of patients had serological evidence of past or present hepatitis B virus infection. Median duration of survival was seven weeks from diagnosis. Only the presence or absence of cirrhosis and clinical condition at diagnosis affected prognosis. The majority of tumours were of trabecular histological pattern and liver cell dysplasia was noted in the non-neoplastic liver of 79% of patients. Chapters 2 and 3. The treatment of HCC is reviewed and a phase II clinical trial of treatment with the cytotoxic drug mitozantrone reported. Objective responses to mitozantrone treatment were seen in 27% of evaluable patients and serious side-effects were rare. Quality of survival on treatment was good. Chapter 4. The history of the athymic mouse and the role of this animal in the screening of new anti-cancer therapies is briefly discussed. The "materials and methods" used in the culture of human HCC cell lines and the production of human HCC tumour xenografts are described. Chapter 5. The effects of human lymphoblastoid interferon (HuIFN-o< [Ly], IFN) on the growth of the HCC cell line PLC/PRF/5 were assessed both in vitro and in athymic mice with PLC/PRF/5-derived tumour xenografts. In vitro, PLC/PRF/5 cells were sensitive to the antiproliferative effects of IFN, growth inhibition being noted at concentrations as low as 1.25 IU/ml, and in vivo, IFN reduced tumour xenograft growth rate and prolonged survival in tumour-bearing animals. Further studies examining some of the possible mechanisms involved in growth inhibition in vivo demonstrated that IFN was capable of inducing the enzyme 2,5-oligoadenylic acid synthetase, an inhibitor of protein synthesis, in tumour tissue but not in mouse tissue, and that IFN enhanced the display of HLA class I glycoproteins on tumour cells. Chapter 6. The cytotoxic activity of Natural Killer (NK) cells, which are large granular mononuclear cells of potential importance in the host defence against malignancy, was measured in patients with HCC. Their NK cell activity was found to be reduced when compared to that of healthy control subjects or patients with cirrhosis alone. IFN, at low concentrations, was capable of augmenting the NK cell activity of HCC patients when administered both in vitro and in vivo. Chapter 7. Specimens of normal adult human liver and tumour xenografts derived from three human HCC cell lines were examined for the presence of nuclear androgen receptors. Receptors were detected in both benign and malignant tissue, and at similar concentrations ranging from 235-550 fMol mg DNA. Castration did not alter significantly the subsequent development and growth of HCC tumour xenografts in male athymic mice inoculated with cells from the PLC/PRF/5 cell line. Chapter 8. A monoclonal antibody, K-PLC.

• Item Type: Thesis (MD)
• Qualification Level: Doctoral
• Keywords: Medicine
• Date of Award: 1987
• Depositing User: Enlighten Team
• Unique ID: glathesis:1987-76661
• Copyright: Copyright of this thesis is held by the author.
• Date Deposited: 19 Nov 2019 13:57
• Last Modified: 19 Nov 2019 13:57
• URI: https://theses.gla.ac.uk/id/eprint/76661