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Biomedical subjects

A S Belldegrun

Publications and source records attributed to A S Belldegrun.

At least 19 recordsLinked to original sources
PubMed2001

Improved prognostication of renal cell carcinoma using an integrated staging system.

PURPOSE: To integrate stage, grade, and Eastern Cooperative Oncology Group (ECOG) performance status (PS) into a clinically useful tool capable of stratifying the survival of renal cell carcinoma (RCC) patients. PATIENTS AND METHODS: The medical records of 661 patients undergoing nephrectomy at University of California Los Angeles between 1989 and 1999 were evaluated. Median age was 61 years, male-to-female ratio was 2.2:1, and median follow-up was 37 months. Survival time was the primary end point assessed. Sixty-four possible combinations of stage, grade, and ECOG PS were analyzed and collapsed into distinct groups. The internal validity of the categorized was challenged by a univariate analysis and a multivariate analysis testing for the accountability of each UCLA Integrated Staging System (UISS) category against independent variables shown to have impact on survival. RESULTS: Combining and stratifying 1997 tumor-node-metastasis stage, Fuhrman's grade and ECOG PS resulted in five survival stratification groups designated UISS, and numbered I to V. The projected 2- and 5-year survival for the UISS groups are as follows for the groups: I, 96% and 94%; II, 89% and 67%; III, 66% and 39%; IV, 42% and 23%; and V, 9% and 0%, respectively. UISS accounted for the significant variables in the variate analysis. CONCLUSION: A novel system for staging and predicting survival for RCC integrating clinical variables is offered. UISS is simple to use and is superior to stage alone in differentiating patients' survival. Our data suggests that UISS is an important prognostic tool for counseling patients with various stages of kidney cancer. Further prospective large-scale validation with external data is awaited.

Adult↗
PubMed2001

Dendritic cell-based immunotherapy of renal cell carcinoma.

Although mostly resistant to cytotoxic therapy, renal cell carcinoma has been a testing ground for immunotherapy. The approval of interleukin-2 for the treatment of renal cell carcinoma was a landmark "proof of principle" which showed that agents working solely via the immune system can cause durable cancer remission. Dendritic cells are central to immune-mediated surveillance and destruction of abnormal cells. They possess all the components required to educate immune effector cells that can then mediate tumor destruction. In vitro strategies to expand and load dendritic cells with antigens have now led to human vaccine trials in renal cell carcinoma and other malignancies.

Carcinoma, Renal Cell↗
PubMed2001

Molecular-based therapies for renal cell carcinoma.

The incidence of renal cell carcinoma (RCC) is rising steadily, but the ability to cure patients with metastatic RCC unfortunately remains limited. Emerging interest in gene therapy performance and safety is expressed by patients, medical institutes, and other agencies. It has become evident that better understanding of the genetic impairments and immune pathophysiology in RCC is essential for future improvement in patient care. Clinical trials now underway that are focusing on genetic and immune impairments will hopefully lead to future breakthroughs in RCC therapy. This paper reviews available gene therapies and other related therapeutic approaches for RCC and lists some of the current clinical trials focused on molecular-based therapies.

Carcinoma, Renal Cell↗
PubMed2001

Immunotherapy of prostate cancer.

The realization that prostate cancer is an immunogenic tumor, in conjunction with the discovery of novel methods for priming the immune system to generate an antitumor response, has resulted in several new approaches for prostate cancer immunotherapy. Based on these various approaches, several human clinical trials have begun using immune-based therapies for prostate cancer. These approaches can be divided into cytokine-based therapies, tumor-associated antigen-based therapies, tumor vaccines, and dendritic cell-based therapies. This review summarizes the latest findings from each of these approaches and gives results from the few completed human clinical trials.

Humans↗
PubMed2001

Prostate cryoablation using direct transperineal placement of ultrathin probes through a 17-gauge brachytherapy template-technique and preliminary results.

OBJECTIVES: To describe a new surgical approach to third-generation cryoablation of the prostate and present our preliminary results. METHODS: The technique is detailed and demonstrated in a Web-based video- clip tutorial. Ninety-two men underwent prostate cryoablation (71 primary ablations, 19 salvage procedures, and 2 repeated cryoablations), using direct transperineal placement of ultrathin probes through a 17-gauge brachytherapy template. RESULTS: No fistulous or major complications were observed. Eight patients (8.3%) had minor complications. In 36 patients, the follow-up period was long enough to permit nadir prostate-specific antigen (PSA) evaluation. In 31 (86%), the nadir PSA was 0.5 ng/mL or less. In 5 patients, the nadir PSA was greater than 0.5 ng/mL. The workup revealed systemic failure in 3 patients and inadequate eradication of the prostate gland in 2 patients. In 18 (86%) of 21 androgen-ablation-naive patients, the nadir PSA was 0.5 ng/mL or less. Nine (43%) had an undetectable nadir PSA and 3 had a nadir PSA of greater than 0.5 ng/mL. CONCLUSIONS: A modified, less-invasive approach to cryoablation of the prostate is presented. The preliminary results do not show an increased rate of complications compared with other published series. The clinical outcome data are preliminary. Longer follow-up data are required to draw conclusions concerning efficacy.

Aged↗
PubMed2001

Prognostic factors and molecular markers for renal cell carcinoma.

Renal cell carcinoma is the most common cancer in the kidney, affecting nearly 30,000 Americans every year and is associated with over 12,000 deaths annually. If detected early, renal cell carcinomas can be cured surgically. However, once metastatic disease develops the prognosis for long-term survival is poor. Unfortunately, one-third of patients have metastatic disease at the time of diagnosis and approximately 50% of the patients undergoing surgical resection for less advanced disease eventually relapse. This review examines the clinical and molecular prognostic tools currently available or under investigation for kidney cancer.

Biomarkers, Tumor↗
PubMed2001

Laparoscopic radical nephrectomy.

Most of the open renal procedures have been duplicated or approximated by laparoscopy. Past concerns about increased operative time, cost, resection completeness, and port site metastases are being overruled or put into perspective as experience with laparoscopic radical nephrectomy (LRN) is gained: necessary skills can be acquired, operative times are approaching those for open procedure, and a 14% difference in cost is counterbalanced by reduced postoperative expenditures. Moreover, LRN is acknowledged by its quality-of-life advantages-reduced morbidity and improved cosmetic outcome. Disease-free rate with LRN at last follow-up is 100% for TNM stage I and 89% +/- 6.6 for stage II (1997 classification). Complications are acceptable with an 8% to 35% incidence of minor complications and a 3% to 19% incidence of severe complications. Conversion to an open procedure occurs in 0% to 10% of cases. The procedure's limitations and the appropriate criteria for patient selection are evident. The learning process is believed to last for approximately 20 procedures and patient selection is based on both clinical criteria and one's insight on his location on the learning curve. Therefore, LRN is becoming the treatment of choice for most TNM stages I and II renal tumors. Moreover, recent data advocating pre-immunotherapy nephrectomy in metastatic patients may permit laparoscopic nephrectomy to further benefit selected metastatic patients by potentially shortening the time interval from nephrectomy to immunotherapy and improving immune responsiveness.

Carcinoma, Renal Cell↗
PubMed2001

Vaccine and gene therapy of renal cell carcinoma.

The concept of tumor vaccines is not new. However, advances in gene transfer technology, tumor immunology, molecular biology, and methods of monitoring antitumor response, have allowed for novel, more specific vaccine approaches. For example, first-generation tumor vaccines were composed of whole inactivated cancer cells, or tumor lysates (Tuly) given together with immune adjuvants like bacillus Calmette-Guerin (BCG). Current strategies include tumor cells modified with genes encoding molecules necessary to stimulate a cytotoxic T cell response, such as cytokine genes, foreign HLA genes, tumor-associated antigen (TAA) genes, and even costimulatory molecules. Activation of cellular immunity requires at least three synergistic signals including presentation of specific tumor antigens, costimulatory signals (B7 molecules), and propagation of the immune response via cytokine release. In general, tumor cells often fail to demonstrate any of these immunostimulatory properties. Dendritic cell-based vaccines are gaining popularity as these cells can properly present TAA to the immune system, thus circumventing the poor antigen-presenting qualities of tumor cells. Dendritic cells can be "loaded" with TAA or other molecules either by their natural endocytotic capabilities, or by genetic modification.

Carcinoma, Renal Cell↗
PubMed2001

Reevaluation of the 1997 TNM classification for renal cell carcinoma: T1 and T2 cutoff point at 4.5 rather than 7 cm. better correlates with clinical outcome.

PURPOSE: We analyzed the effects of the change in TNM classification from the 1987 to the 1997 version and suggest a modified tumor size cutoff point between T stages 1 and 2 for renal cell carcinoma. MATERIALS AND METHODS: We evaluated a database containing the records of 661 patients who underwent nephrectomy between 1989 and 1999. The effect of the change in TNM classification on the distribution of patients between stages, the rates of M+ and N+ disease, and the local and distant recurrence rates were outlined for 280 patients with T stages 1 and 2 disease. The Cox model was used to identify the optimal cutoff point between T1 and T2 disease, and the resulting effect of adopting this cutoff was outlined. RESULTS: A total of 174 and 128 cases were down staged from 1987 version stage T2 to 1997 version stage T1 and from 1987 TNM stage II to 1997 TNM stage I, respectively. Survival was not significantly different in patients with 1997 TNM stages I and II disease due to a lack of survival difference during the first 2 years of followup. Stage shift also caused an increase in average tumor size, the proportion of patients with high grade cancer, and M+ and N+ disease at diagnosis in 1997 stages T1 and T2 as well as an increase in the proportion of 1997 stage T2N0M0 cases at diagnosis with systemic failure. Analysis of 11 potential cutoff points between 1 and 10 cm. revealed that 4.5 cm. was most predictive of patients survival (hazards ratio 4.99, p = 0.0001). Using this cutoff resulted in improved discriminatory power of the TNM classification and a moderating effect on the distribution of patients, average tumor size, high grade disease, M+ and N+ disease at diagnosis, and systemic failure between T(14.5) and T(24.5) compared with 1997 T1 and T2. CONCLUSIONS: Our data imply that the current cutoff point of 7 cm. between stages T1 and T2 tumors is too high. Lowering the cutoff to 4.5 cm. resulted in better discriminatory power of the TNM classification in our dataset. This observation should be further validated by external data.

Adult↗
PubMed2001

The changing natural history of renal cell carcinoma.

PURPOSE: Our understanding of the natural history of renal cell carcinoma, the role of nephrectomy, the benefits of immunotherapy and the possibilities of new technologies are evolving and being integrated with advances in classification and staging. We reviewed the relevant literature to clarify these pertinent questions and provide a current review of the changes in the epidemiology, treatment and prognosis of patients with renal cell carcinoma. MATERIALS AND METHODS: We comprehensively reviewed the peer reviewed literature on the current management of and results of treatment for renal cell carcinoma. RESULTS: The incidence of and mortality from renal cell carcinoma have continuously increased during the last 50 years. Despite this increase in the number of new patients and consequently the number of deaths yearly the percent of those surviving for 5 years has notably improved. Factors related to improved survival include advances in renal imaging, earlier diagnosis, improved staging, better understanding of prognostic indicators, refinement in surgical technique and the introduction of immunotherapy approaches for advanced disease. CONCLUSIONS: Currently patients with localized and metastatic renal cell carcinoma have had improvements in outlook and the therapeutic options available have expanded.

Carcinoma, Renal Cell↗
PubMed2000

Gene therapy for prostate cancer at the University of California, Los Angeles: preliminary results and future directions.

The treatment options for patients with advanced prostate cancer are limited. Because of recent advances in the understanding of the molecular biology of prostate cancer, the accessibility of the prostate for injection, and the availability of gene promotors that allow tissue-specific expression of therapeutic gene products, gene therapy for prostate cancer has realized significant achievements in recent years. What once belonged to the realm of basic science is now entering the domain of phase II clinical trials. In this review, current results and future directions in prostate gene therapy at the University of California, Los Angeles, are discussed.

California↗
PubMed2000

Intermittent androgen deprivation therapy: schedule modifications based on a novel in vivo human xenograft model.

In most clinical trials of intermittent androgen deprivation (IAD), the decision to stop androgen withdrawal is based on monitoring PSA levels, waiting for its drop to nadir. Based on in vitro pre-clinical studies, a modified 'on-off' schedule of short intervals of androgen deprivation, designated pulsed androgen deprivation (PAD), is proposed to destroy androgen dependent (AD) cells more gradually and to conserve their androgen-independent (AI) inhibitory potential for longer periods, resulting in an overall prolongation of time to hormone resistant progression.Prostate Cancer and Prostatic Diseases (2000) 3, 280-282

Journal Article↗
PubMed2000

CL1-GFP: an androgen independent metastatic tumor model for prostate cancer.

PURPOSE: The mechanisms responsible for tumor progression to androgen independence in prostate cancer (CaP) remain unknown. To characterize these changes and provide a basis for rational therapeutic strategies for advanced CaP, an in vivo model from a highly aggressive androgen independent CaP cell line with distinct cellular and molecular properties was developed. MATERIALS AND METHODS: An aggressive androgen-independent cell line designated CL1 was derived from a slow-growing, and androgen-dependent, parental LNCaP cell line through in-vitro androgen-deprivation and selection. CL1 was stably transfected with a green fluorescence protein gene (CL1-GFP) and orthotopically injected into SCID mice. The pathologic behavior, histology, and molecular determinants of CL1 tumor and metastases were determined and characterized by standard light and fluorescent microscopy, and quantitative RT-PCR analysis. RESULTS: CL1 is an anaplastic prostate cancer cell line which demonstrates extensive local invasion and metastases to various organs that can be visualized via GFP expression. When compared with parental LNCaP cells, RT-PCR analysis of the tumor revealed an over-expression of EGFR, b-FGF, VEGF, TGF-beta, IL-8, IL-6, and bcl-2 and a down regulated expression of the p53, E-cadherin and PTEN. In contrast to LNCaP cells, CL1 tumors express lower levels of androgen receptor and barely detectable PSA mRNA. CONCLUSIONS: CL1-GFP represents an aggressive androgen-independent CaP tumor model derived through androgen deprivation whose pathologic development and molecular properties in animals resembles the clinical characteristics of hormone refractory prostate cancer (HRPC). Metastatic sites of CL1-GFP can be visualized with fluorescence microscopy offering a unique therapeutic model for the evaluation of drug sensitivity and other therapeutic modalities.

Androgens↗