Biomedical subjects

A R Bateman

Publications and source records attributed to A R Bateman.

4 recordsLinked to original sources

PubMed2001

Gene therapy for prostate cancer: current status and future prospects.

PURPOSE: Locally advanced, relapsed and metastatic prostate cancer has a dismal prognosis with conventional therapies offering no more than palliation. In recent years advances achieved in understanding the molecular biology of cancer have afforded clinicians and scientists the opportunity to develop a range of novel genetic therapies for this disease. MATERIALS AND METHODS: We performed a detailed review of published reports of gene therapy for prostate cancer. Particular emphasis was placed on recent developments in the arena of nonviral (plasmid DNA, DNA coated gold particles, liposomes and polymer DNA complexes) and viral (adenovirus, retrovirus, adeno-associated virus, herpes virus and pox virus) vectors. Therapeutic strategies were categorized as corrective, cytoreductive and immunomodulatory gene therapy for the purpose of data analysis and comparison. RESULTS: Locoregional administration of nonviral and viral vectors can yield impressive local gene expression and therapeutic effects but to our knowledge no efficient systemically delivered vector is available to date. Corrective gene therapy to restore normal patterns of tumor suppressor gene (p53, Rb, p21 and p16) expression or negate the effect of mutated tumor promoting oncogenes (ras, myc, erbB2 and bcl-2) have efficacy in animal models but this approach suffers from the fact that each cancer cell must be targeted. A wide variety of cytoreductive strategies are under development, including suicide, anti-angiogenic, radioisotopic and pro-apoptotic gene therapies. Each approach has strengths and weaknesses, and may best be suited for use in combination. Immunomodulatory gene therapy seeks to generate an effective local immune response that translates to systemic antitumor activity. Currently most studies involve immunostimulatory cytokine genes, such as granulocyte-macrophage colony-stimulating factor, or interleukin-2 or 12. CONCLUSIONS: Various therapeutic genes have proved activity against prostate cancer in vitro and in vivo. However, the chief challenge facing clinical gene therapy strategies is the lack of efficient gene delivery by local and systemic routes. For the foreseeable future vector development may remain a major focus of ongoing research. Despite this caveat it is anticipated that gene therapy approaches may significantly contribute to the management of prostate cancer in the future.

Adjuvants, Immunologic↗

PubMed2000

Cancer gene therapy: developments to 2000.

Cancer, at the molecular level, continues to be more thoroughly understood. With this understanding comes the opportunity for innovative therapeutic intervention. Gene therapy remains an attractive concept to treat cancer. However, a number of gene therapy clinical trials have now been reported and it is clear that barriers remain before gene therapy gains widespread clinical application. This article outlines current directions and novel developments in the field of cancer gene therapy, which attempt to overcome these obstacles.

Animals↗

PubMed1997

Cancer-related thromboembolic disease in patients with solid tumours: a retrospective analysis.

BACKGROUND: Cancer patients frequently suffer thromboembolic events. This study assessed the incidence and resource implications of cancer-related thromboembolic disease (CTD) in a single, large cancer centre. PATIENTS AND METHODS: A retrospective analysis of patients admitted with CTD and/or the complications of treatment of CTD over a two-year period has been conducted. Forty-eight patients (23 male, 25 female, median age 60 years) with a variety of solid tumours were identified. RESULTS: The initial presentations were venous thromboses (28 patients) and pulmonary embolism (20 patients). The median interval from cancer diagnosis to the initial episode of CTD was eight (range 0-112) months. Twenty-two patients suffered additional thromboses, despite maintenance warfarin anticoagulation in 18 patients. Six patients experienced anticoagulation-induced haemorrhage. Forty-one (85.4%) patients have died. The median survival from the first thromboembolic event was 8.5 months. The median inpatient stay for management of the first event was 10 (range 4-75) days, accounting for 729 inpatient days during the study period. Recurrent episodes of CTD or complications of anticoagulation resulted in 28 readmissions, accounting for 295 inpatient days. During the two-year period 1024 inpatient days were directly caused by CTD and its complications, representing 6.1% bed occupancy on our unit. CONCLUSION: This study demonstrates that CTD represents a significant cause of morbidity in cancer patients with considerable resource implications for cancer centres. Improvements in prevention and management of CTD would reduce morbidity and lead to considerable cost savings.

Adult↗

PubMed1995

Risk factors for pneumothorax during percutaneous Hickman line insertion in patients with solid and haematological tumours.

The purpose of this study was to identify risk factors for pneumothorax during percutaneous subclavian Hickman line insertion in patients with haematological (HT) or solid tumours (ST). One hundred and twelve patients (55 HT, 57 ST) had 132 subclavian Hickman lines inserted under fluoroscopic control. Lines were inserted on the left on 116 occasions and the right in 16. Thirty-five single, 29 double and 68 triple lumen catheters were inserted. Variables included in the analysis were age, sex, side of insertion, catheter gauge and nutritional status as indicated by the body mass index (BMI kg/m2). Both univariate and logistic regression analyses were performed. There were ten pneumothoraces, all occurring in patients with STs. Univariate analysis revealed that patients with STs were older (median age 59 versus 36 years; P = 0.0001) and more cachectic (median BMI 21.9 versus 24.2 kg/m2; P = 0.03) than those with HTs, and the patients experiencing pneumothorax were older (median age 57 versus 44 years; P < 0.01) and more cachectic (median BMI 19.6 versus 24.0 kg/m2; P = 0.004) than those undergoing uncomplicated procedures. For patients with a BMI < 19 kg/m2 versus those with a BMI > 19 kg/m2, the pneumothorax rate was 5/8 versus 5/124 (P < 0.00001). Logistic regression analysis confirmed the significantly older age of the patients with STs (P < 0.001) and of those experiencing pneumothorax (P = 0.02). This analysis also confirmed the lower BMI of patients experiencing pneumothorax (P = 0.002). The patients' sex, the side of line insertion and the catheter gauge were not associated with pneumothorax on either the univariate or logistic regression analyses. From these data we conclude that pneumothorax complicating a subclavian Hickman line is significantly more likely in elderly patients with a low BMI. Such patients are more likely to have STs than HTs. In patients with a BMI < 19 kg/m2, the subclavian route should be used with caution.

Adult↗