Biomedical subjects
Publications and source records attributed to Christopher S D Lee.
We report on the incorporation of microfluidic structure within a high-water-content hydrogel [4% (w/v) calcium alginate]. We used the microfluidic network to control the chemical environment within the hydrogel and demonstrated higher rates of delivery and extraction of solutes than was achievable by diffusion alone.
PURPOSE: The 4th annual meeting of the Society of Urologic Oncology (SUO) was held December 5-6, 2003 in Bethesda, Maryland. The meeting was attended by urologists, medical and radiation oncologists, and researchers whose focus is genitourinary (GU) malignancies. More than 500 participants registered for the meeting. MATERIALS AND METHODS: The agenda for the SUO meeting included more than 50 speakers and discussion panels, and addressed a broad range of topics in GU oncology. Transcripts of the proceedings and submitted slide presentations were reviewed for content following the meeting, and the highlights were summarized. These written materials can be accessed through the SUO web site at http://societyofurologiconcology.org. RESULTS: Reviewed session topics included epidemiology of GU malignancies, biomarkers for GU malignancies, cancer genomics, bladder cancer, testis cancer, minimally invasive treatments for GU malignancies, molecular therapeutics and advanced prostate cancer. Significant advances in these fields have directly impacted clinical care and improved patient outcomes across the many disciplines associated with treatment of GU cancers. CONCLUSIONS: The SUO meeting is unique in its multidisciplinary forum and focus on urological oncology. The 2003 meeting highlighted recent advances in epidemiology, clinical management and emerging molecular approaches in the diagnosis and treatment of urological malignancies with several state-of-the-art presentations.
Recombinant interleukin-2 (IL-2) has demonstrated antitumor activity and durable clinical responses in patients with metastatic melanoma. Careful screening and selection of appropriate patients has improved the safety profile of IL-2 administration. Gross hematuria would ordinarily preclude the safe delivery of IL-2. We report a case of metastatic melanoma to the bladder presenting with hematuria. A complete resection was performed and subsequently allowed the administration of high-dose, bolus IL-2. The combination of resection and IL-2 therapy resulted in a partial response maintained for more than 18 months. Symptomatic bladder melanoma should be aggressively treated to allow for systemic immunotherapy, which can provide durable responses.
Identification of novel tumor-associated antigens (TAA) capable of eliciting T-cell responses has renewed interest in the development of anti-tumor vaccines. The insertion of genes encoding specific TAA into a vaccinia virus (rVV) is one approach to vaccination since large amounts of foreign DNA can be stably integrated into the poxvirus genome. Recent reports have documented an increased therapeutic effectiveness of poxvirus-based vaccines when additional treatment with cytokines, such as interleukin-2 (IL-2) or interleukin-12 (IL-12) were used, but the combination of these cytokines as adjuvants for a rVV encoding TAA have not been previously reported. The combination of IL-2 and IL-12 at single regimen systemic doses was toxic and sometimes fatal, manifesting largely as segmental epithelial apoptosis of the large bowel. To explore the local delivery of both cytokines to the site of vaccination, the genes encoding IL-2 and IL-12 were inserted into vaccinia virus along with a model tumor antigen gene. This construct contained five heterologous genes: LacZ (the model antigen), gpt (reporter gene), IL-2, and the two IL-12 subunit genes (p35 and p40). Treatment with this recombinant virus resulted in a reduced number of pulmonary metastases, improved survival, and minimal toxicity in a murine tumor model. The use of vaccinia virus for the insertion of other heterologous gene combinations may provide a powerful and less toxic approach for novel vaccination strategies in the treatment and prevention of cancer.
Prostate cancer is the most common malignant tumour in men and there are few treatment options available once the tumour becomes refractory to hormonal manipulation. Prostate-specific antigen (PSA) is a secretory glycoprotein that is commonly expressed by prostatic epithelial cells and is found in elevated levels in the serum of men with prostate cancer. The identification of T cell specific epitopes within the coding sequence of PSA has led to the development of various vaccine strategies that target PSA in an attempt to treat established prostate cancer. These strategies have included human leukocyte antigen-restricted PSA peptides, dendritic cells pulsed with PSA, recombinant viruses expressing PSA and combinations of different vectors. In addition to PSA, several other antigens have been described that may be useful for targeting prostate tumours by vaccines. Animal studies have established the feasibility and safety for many of these agents and clinical trials are now in progress to evaluate the immunological and clinical responses of PSA vaccines. Further research in manipulating anti-PSA immunity with cytokines, costimulatory molecules and other immune modulating agents will likely improve the therapeutic effectiveness of PSA vaccines. Clinical trials designed to evaluate the effects of vaccination in different stages of disease and through different routes of administration need to be performed to define the optimal schedule for PSA vaccines in patients with prostate cancer, or for those at high risk of developing the disease.