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Biomedical subjects

M A Burton

Publications and source records attributed to M A Burton.

At least 19 recordsLinked to original sources
PubMed2001

Tumour dosimetry in human liver following hepatic yttrium-90 microsphere therapy.

Radiation dose distributions arising from intrahepatic arterial infusion of 90Y microspheres have been investigated. Tissue samples from normal liver, the tumour periphery and tumour centre were taken from a patient following infusion of 3 GBq of 32 microm diameter resin microspheres labelled with 90Y as treatment for an 80 mm diameter metastatic liver tumour. The measured microsphere distributions in three dimensions were used to calculate radiation dose patterns. Although microspheres concentrated in the tumour periphery, heterogeneous doses were delivered to all tissues. Within the tumour periphery average doses ranged from 200 Gy to 600 Gy with minimum doses between 70 Gy and 190 Gy. The average and minimum doses for the tumour centre sample were 6.8 Gy and 3.7 Gy respectively. In the normal liver sample the average dose was 8.9 Gy with a minimum dose of 5 Gy. Less than 1% of the normal liver tissue volume received more than 30 Gy, the level above which complications have resulted for whole liver exposure using external beam radiotherapy. These calculations suggest that preferential deposition of microspheres in the well-vascularized periphery of large tumours will lead to a high proportion of the tumour volume receiving a therapeutic dose, with most of the normal liver tissue being spared substantial damage.

Biophysical Phenomena↗
PubMed2000

Analysis of the distribution of intra-arterial microspheres in human liver following hepatic yttrium-90 microsphere therapy.

The microscopic distribution of microspheres in human liver following hepatic infusion of 32 microm diameter resin microspheres labelled with 90Y as treatment for an 80 millimetre diameter liver cancer has been investigated. Microspheres were found to deposit inhomogeneously in tissues, preferentially lodging in a region approximately 6 mm wide around the periphery of the tumour. A relative concentration of microspheres of 50 to 70 times that of normal hepatic parenchyma and 65 to 94 times that in the tumour centre was measured in this region. The deposition of spheres in the tumour periphery was not uniform, and cluster analysis showed that the spheres could be classified into clusters. The number of microspheres in a cluster was skewed towards low numbers and cluster sizes varied from 20 to 1500 microm. The observed deposition patterns indicate that the vascular tumour periphery will receive much greater radiation doses from radioactive microspheres than both normal tissue and the avascular tumour centre.

Arteries↗
PubMed1999

Lipoplexes and tumours. A review.

The need for genotherapy to refocus its attention on to laboratory evaluation of better methods rather than proceeding to the clinic with semi-apt tools for genetic transfer has been highlighted in clinical study reports documented to date. Quintessential for tumour genotherapy is the ability to target abnormal cells, hence reducing exposure of normal cells to genetic material whilst maximizing gene dosage to tumour cells. This becomes increasingly important as genotherapy establishes itself in the clinic alongside the older modes of treatment. This review has discussed the applicability of lipoplexes for genotherapy of solid tumours. Lipoplexes have been used extensively for gene transfer into cells, such as cancerous cells, deficient for a certain gene product. While cationic liposomes have many advantages over other forms of delivery mechanisms, several problems hinder their use in-vivo. A closer examination of the physical limitations of current lipoplex preparations, the development and testing of novel formulations, combined with more attention to the cellular processes of cell membrane breaching and nuclear entry, may enhance gene delivery. Essential for tumour genotherapy is the ability to target these lipoplexes into tumour sites whilst reducing gene dosage to other normal tissues. Development of a better lipofection agent may indeed require a collaboration of the fields of physiology, cell biology, molecular biology, biochemistry, chemistry and membrane physics.

Animals↗
PubMed1998

A comparison of two computer-based face identification systems with human perceptions of faces.

The performance of two different computer systems for representing faces was compared with human ratings of similarity and distinctiveness, and human memory performance, on a specific set of face images. The systems compared were a graph-matching system (Lades M, Vorbrüggen JC, Buhmann J, Lage J, von der Malsburg C, Würtz RP, Konen W. IEEE., Trans Comput 1993;42:300-311.) and coding based on principal components analysis (PCA) of image pixels (Turk M, Pentland A. J Cognitive Neurosci 1991;3:71-86.). Replicating other work, the PCA-based system produced very much better performance at recognising faces, and higher correlations with human performance with the same images, when the images were initially standardised using a morphing procedure and separate analysis of 'shape' and 'shape-free' components then combined. Both the graph-matching and (shape + shape-free) PCA systems were equally able to recognise faces shown with changed expressions, both provided reasonable correlations with human ratings and memory data, and there were also correlations between the facial similarities recorded by each of the computer models. However, comparisons with human similarity ratings of faces with and without the hair visible, and prediction of memory performance with and without alteration in face expressions, suggested that the graph-matching system was better at capturing aspects of the appearance of the face, while the PCA-based system seemed better at capturing aspects of the appearance of specific images of faces.

Adult↗
PubMed1998

University performance, gender and the rural health workforce: an analysis of nursing students.

The relationship between student gender and performance was examined in first year students enrolled in the Bachelor of Nursing course at Charles Sturt University from 1991 to 1995. A greater proportion of female students achieved passing grades in subjects studied when compared to male students, irrespective of the subject discipline area. Furthermore, a significantly greater proportion of female than male students passed nursing subjects; however, no statistically significant differences in performance were detected in the proportion of male or female students in either science or humanities subjects.

Education, Nursing, Baccalaureate↗
PubMed1997

The efficacy of doxorubicin microspheres for hepatic micrometastases in a rat tumour model.

The use of sustained-release microspheres is of potential benefit as an adjuvant treatment for patients with occult hepatic micrometastases. This study investigates the response of a model of implantable adenocarcinoma micrometastases in the livers of DA rats following the intraportal injection of doxorubicin-incorporated ion-exchange microspheres compared to free drug bolus administration. A point-counting technique was used to determine the percentage of liver consisting of tumour 13 days after treatment. This was used as an indicator of tumour response, as was the derived tumour mass. There was a significantly higher tumour response in animals treated with the microspheres compared to animals treated with free drug delivered at the same concentration. This effect, however, was shown to decrease with a delay in the time of treatment. The tumour response of the sustained-release microspheres was achieved in the absence of any detectable local or systemic toxicity. This study demonstrates the potential of sustained-release microspheres in the treatment of patients with hepatic micrometastases.

Animals↗
PubMed1997

Enhanced anticancer therapy mediated by specialized liposomes.

It has been a central aim of experimental and clinical therapeutics to deliver therapeutic agents as close as possible to, or if possible within, a diseased cell. Such targeting achieves two major aims of drug delivery, the maximum dose of therapeutic agent to the diseased cell and avoidance of uptake by and, usually, accompanying side-effects to normal, healthy cells. Conventional liposomes, originally used for studies in membrane biophysics and biochemistry, have been used in therapy for the past two decades. However, when applied to deliver drugs into cells, conventional liposomes proved inefficient and so novel unconventional or specialized liposomes are constantly being prepared to enhance cell-specific delivery in-vivo. One possible way of achieving better targeting is combination of the positive attributes of more than one specialized type of liposome into one vesicle. Although a limited number of studies has examined the combined effect of such dual-specialty liposomes, more studies are warranted using appropriate models. Liposomes are composed of one, a few, or many concentric bilayer membranes which alternate with aqueous spaces. The drugs are encapsulated within the aqueous internal volume if they are hydrophilic or in the lipid bilayers if they are hydrophobic (Kim 1993). Liposomes range in size from 25 nm to more than 20 microns (Sugarman & Perez-Soler 1992). Depending on their solubility and method of formulation antimicrobial, cytotoxic and other conventional drugs, hormones, antigens, enzymes, genetic material, viruses and bacteria can be incorporated in either the aqueous or hydrophobic phase. This review discusses the types and characteristics of non-conventional liposomes used in various modes of cancer therapy, mainly chemotherapy and gene therapy. It concludes with suggestions on improving these novel liposomal to effect better targeting to cancer cells.

Animals↗
PubMed1996

Tumour cells surviving in vivo cisplatin chemotherapy display elevated c-myc expression.

The c-myc oncogene has been extensively implicated in cell proliferation, cell differentiation and programmed cell death. Aberrant expression of the c-myc gene product has been observed in a range of tumours and has also been implicated in cisplatin (cis-dichlorodiammineplatinum)-mediated chemoresistance. A solid transplantable tumour model in syngeneic DA rats was subjected to treatment with cisplatin to determine the impact of such therapy on endogenous c-myc gene expression. Serially transplanted tumours were intravenously treated with a single cisplatin dose (1 mg/kg) and c-myc expression analysed 2 and 7 days after treatment. The surviving tumour cells display a significant 2-fold elevation in c-myc expression at 48 h and 7 days after treatment. Primary cell cultures have been derived from untreated in vivo tumours of the same model and subjected to treatment with a c-myc phosphorothioate antisense oligomer. Administration of 5 microM c-myc antisense oligomer directed at the initiation codon and first four codons of c-myc mRNA results in total inhibition of c-myc expression and coincident suspension of cell growth for a period of 4 days in culture. Antisense therapies directed at the c-myc gene may well prove an effective tool for treating tumours in conjunction with cisplatin as these findings show that tumour cells surviving cisplatin chemotherapy display elevated c-myc expression.

Animals↗
PubMed1996

The basis for somatic gene therapy of cancer.

A decade of advances in understanding of the molecular basis of sporadic and familial cancers has combined with developments in mammalian gene transfer technology to stimulate intensive research into the potential applications of somatic gene therapy for cancer. Somatic gene immunotherapy is already in progress to stimulate and direct the natural targeting capabilities of the immune system against the threat of disseminated residual disease. The association of a plethora of mutated tumor suppressor genes (p53, p16 BRCA1, BRCA2) with diverse cancers has also highlighted the potential of somatic gene therapy with wild-type versions of suppressor genes as an anti-cancer therapeutic modality either in its own right or in synergistic association with traditional anti-cancer therapies. The methodologies for gene transfer technology range from direct intravenous injection of naked modified DNAs to intravenous injection of liposome-encapsulated DNAs or microsphere-bound DNAs. Recombinant retroviral and adenoviral vectors have natural transfection capabilities and display tropism for particular tissues that are of selective advantage against particular cancers. Liposomes display very high efficiencies of gene transfer with the advantages of successful transfer to a wide range of tissue types but their widespread systemic distribution offers problems in relation to selective targeting of tumor cells. The challenges to current gene transfer processes are much the same as that of other anti-cancer therapies: achieving selective targeting of cancer cells whilst optimizing dosages and minimizing the risk of collateral damage to healthy tissues.

Animals↗
PubMed1995

Adjuvant internal radiation therapy in a model of colorectal cancer-derived hepatic metastases.

Selective internal radiation therapy (SIR therapy) is a technique whereby metastatic liver cancer is irradiated by embolising microspheres containing the radionuclide yttrium-90 into the hepatic arterial circulation. To date this technique has not been used as an adjuvant therapy, but rather to treat established metastases in the liver. This study evaluated the use of two intrahepatic radiation doses delivered on radioactive microspheres for the treatment of small, growing micrometastases. Three groups of five rats were each inoculated with tumour spheroids into the portal vein. The resultant liver micrometastases were treated with either 10 or 20 MBq of yttrium-90 microspheres or a sham dose of non-radioactive microspheres injected into the portal vein 2 days following tumour inoculation. The livers of each animal were examined for the presence of metastases after a further 21 days and liver function tests were performed. At the time of sacrifice there was no obvious normal liver damage in any of the rats treated with microspheres. The livers of the sham-treated animals contained extensive signs of tumour deposition. A mean of 34 tumours were taken from the livers of each of the sham-treated animals, whereas only a single tumour was found in one animal treated with 10 MBq of yttrium and eight small tumours from two animals treated with 20 MBq. Liver function tests demonstrated a significant short-term increase in alkaline phosphatase levels in the radiation-treated animals compared with shams, but there were no other indications of any effects on liver function. These results indicate a potential role for SIR therapy in an adjuvant setting with colorectal cancer.

Animals↗
PubMed1992

Dose response and toxicity of doxorubicin microspheres in a rat tumor model.

The therapeutic response and toxic effects of chemotherapy using several doses of doxorubicin in conventional solution form or bound to an ion-exchange resin were compared in a rat tumor model, to assess the relationship of drug dose to therapeutic efficacy and associated toxicity. Single bolus injections of 3.0, 4.5, 6.0, 7.5 and 9.0 mg/kg were administered via the abdominal aorta to rats bearing hindlimb tumors. Tumor size was measured serially and the growth rates of treated groups were compared with a control growth curve. In addition, the effect of empty microspheres on tumor growth rate was assessed. The levels of circulating white blood cells were measured and compared to control levels to provide an indication of the severity of bone marrow toxicity experienced by each form of treatment. Finally, any difference in the distribution of doxorubicin to tumor, hindlimb and cardiac tissue following administration of doxorubicin as free drug or on microspheres was ascertained. Empty ion-exchange resin exerted a small although significant detrimental effect on tumor growth which may be explained by the embolization of microspheres in the precapillary blood vessels of the tumor resulting in a transient delay in tumor growth rate. The lowest dose of doxorubicin produced a significantly better therapeutic response when administered in the free drug form, but higher doses elicited an equivalent delay in tumor growth for both drug microsphere and free drug groups in a dose-dependent manner, with the maximum anti-tumor response occurring at the highest dose. Treatment with free doxorubicin at high doses resulted in significant reductions of circulating white blood cells suggesting the occurrence of bone marrow toxicity.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenocarcinoma↗
PubMed1992

Regression of liver metastases following treatment with yttrium-90 microspheres.

Selective internal radiation (SIR) therapy is a technique developed by our group for concentration of Yttrium-90 microspheres into liver metastases. The technique involves laparotomy, insertion of the catheter into the hepatic artery, redistribution of liver blood flow with vaso-active agents and incremental embolization of Yttrium-90 containing microspheres (SIR spheres) into the liver. Twenty-nine patients with non-resectable liver metastases from primary adenocarcinoma of the large bowel were treated by this technique and followed for a minimum of three months to assess evidence of tumour regression. Response to treatment was measured by serial estimations of carcino-embryonic antigen (CEA) and tumour volumes measured from serial computerized tomography (CT) scanning of the liver. There was a fall in the serum CEA level in all 26 patients in whom the serial estimations of CEA were performed following SIR therapy. The overall mean fall in CEA was 70% of pre-treatment levels with 88% of patients (23 of 26) experiencing more than a 50% fall in pre-treatment CEA levels. In 18 of 22 evaluable patients CT measured tumour volumes decreased following SIR therapy. In 48% of patients (10 of 22 patients) the decrease in tumour volume was more than 50%. SIR therapy results in a high rate of tumour regression in patients with liver metastases secondary to large bowel cancer.

Adenocarcinoma↗
PubMed1992

Evaluation of ion-exchange microspheres as carriers for the anticancer drug doxorubicin: in-vitro studies.

A comparison study of doxorubicin loading, release characteristics and stability within sodium and hydrogen forms of ion-exchange resin microspheres has been performed. It was demonstrated that resins in the Na+ form, although having lower drug loading capacity, showed similar release profiles to resins in the H+ form but still maintain all the drug activity. Resins in the H+ form, despite having high drug loading capacity, caused drug degradation within microspheres due to their strong acidic nature. Therefore, in comparison with the H+ form, resins in the Na+ form can be considered as better carriers for doxorubicin in terms of sustaining the release of drug and maintaining drug activity. Other factors such as the degree of resin cross-linkage and drug/resin mixing time have also been examined in relation to drug loading and release characteristics. Overall, this study demonstrated the significance of the characteristics of matrix materials and their influence on the drug activity and microsphere performance in-vitro.

Chromatography, High Pressure Liquid↗
PubMed1991

Dose distribution following selective internal radiation therapy.

Selective Internal Radiation Therapy is the intrahepatic arterial injection of microspheres labelled with 90Y. The microspheres lodge in the precapillary circulation of tumor resulting in internal radiation therapy. The activity of the 90Y injected is managed by successive administrations of labelled microspheres and after each injection probing the liver with a calibrated beta probe to assess the dose to the superficial layers of normal tissue. Predicted doses of 75 Gy have been delivered without subsequent evidence of radiation damage to normal cells. This contrasts with the complications resulting from doses in excess of 30 Gy delivered from external beam radiotherapy. Detailed analysis of microsphere distribution in a cubic centimeter of normal liver and the calculation of dose to a 3-dimensional fine grid has shown that the radiation distribution created by the finite size and distribution of the microspheres results in an highly heterogeneous dose pattern. It has been shown that a third of normal liver will receive less than 33.7% of the dose predicted by assuming an homogeneous distribution of 90Y.

Humans↗