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Biomedical subjects

A J Pantuck

Publications and source records attributed to A J Pantuck.

At least 37 records · Page 2Linked to original sources

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↗

Bladder cancer 2000: molecular markers for the diagnosis of transitional cell carcinoma.

The search continues for better tumor markers to improve the rate of detection of transitional cell carcinoma (TCC) more quickly in larger populations and to predict the possibility of disease recurrence. Among several new tests currently being screened, telomerase and hyaluronic acid/hyaluronidase (HA/HAase) have shown sensitivity and specificity equal to or better than cytology, and other promising tumor markers are being investigated. Although no marker has yet replaced the need to perform cystoscopy and cytology, the new tests can minimize the cost and difficulty of screening and long-term surveillance of patients who have or are at risk for bladder cancer.

Journal Article↗

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↗

Ureteroenteric anastomosis in continent urinary diversion: long-term results and complications of direct versus nonrefluxing techniques.

PURPOSE: Controversy exists over the importance of antireflux mechanisms in large volume, low pressure intestinal bladder substitutions. Despite the theoretical benefits of reflux prevention, antirefluxing ureteral reimplantations may have a greater risk of anastomotic stricture. We hypothesize that this inherent stricture rate may outweigh the potential benefits associated with reflux prevention. To assess this question critically we compare our results to those of direct and nonrefluxing techniques of ureterointestinal anastomosis during continent diversion. MATERIALS AND METHODS: Between 1990 and 1998, 58 patients underwent continent urinary diversion using an Indiana pouch or ileal orthotopic neobladder following cystectomy for muscle invasive bladder cancer. A total of 56 renal units were implanted using an end-to-side Nesbit direct anastomosis and 60 were implanted in a nonrefluxing manner. Clinical end points included anastomotic stricture formation, hydronephrosis, pyelonephritis, upper tract stone formation and renal deterioration, and were assessed with a mean followup of 41 months. RESULTS: Of 60 nonrefluxing ureteroenteric anastomoses 8 (13%) resulted in nonneoplastic stricture formation compared to 1 of 56 (1.7%) direct anastomoses, which was statistically significant (Fisher's exact test p <0.05). Strictures occurred up to 6 years following the original surgery. There was no significant difference between the 2 groups in regard to hydronephrosis, pyelonephritis, upper tract stone formation or azotemia. CONCLUSIONS: Nonrefluxing methods of ureterointestinal reimplantation resulted in a statistically significant higher rate of anastomotic stricture than the end-to-side direct anastomosis. This finding appears to outweigh any theoretical benefits of preventing pyelonephritis, stones or azotemia. For patients undergoing large volume, low pressure continent diversion the refluxing ureterointestinal anastomosis may be the technique of choice since it preserves renal function as well as the nonrefluxing method, is technically easier to perform and poses less risk of stricture. Delayed stricture formation years after surgery underscores the necessity for long-term radiological followup in patients following continent diversion.

Adult↗

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↗

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↗

Immune and genetic therapies for advanced renal cell carcinoma.

Although we have witnessed advances in many aspects of cancer research and therapy in recent years, the ability to cure the majority of patients with advanced renal cell carcinoma (RCC) remains elusive. At the same time, it has become increasingly apparent that a better understanding of the genetic alterations and immune dysregulations in RCC will play a key role in finding a treatment. Therefore, clinical trials directed at specific genetic alterations and studies exploiting components of the immune system are being conducted. These studies provide new hope for an improved outlook for patients presenting with advanced RCC. The future prospects of RCC therapy will be, without doubt, built on the foundation of current investigative efforts in gene and immune therapy. This article reviews the current role of immunotherapy and gene therapy in the management of metastatic RCC. Finally, current clinical trials focusing on gene and immune therapies are listed.

Journal Article↗

Female urethral adenocarcinoma: immunohistochemical evidence of more than 1 tissue of origin.

PURPOSE: Urethral adenocarcinoma is a rare malignancy whose origin remains controversial. The monoclonal antibody mAbDas1 (formerly 7E12H12) was developed against a unique colonic epithelial epitope and is reactive in areas of intestinal metaplasia. Recently the antibody was shown to react in cystitis glandularis as well as adenocarcinoma of the bladder, suggesting that cystitis glandularis may be the precursor of bladder adenocarcinoma. We examined urethral adenocarcinomas and benign urethral specimens using mAbDas1 to determine whether it could provide insight into their histogenesis. MATERIALS AND METHODS: Archival tissue from 12 cases of primary female urethral adenocarcinoma and urethral specimens of inflamed urethral mucosa, urethritis glandularis and transitional cell carcinoma was studied. Immunohistochemical analysis of formalin fixed, paraffin embedded archival tissue was done using the monoclonal antibody mAbDas1. Tumors were also evaluated with a prostate specific antigen (PSA) polyclonal antibody as previous studies have noted PSA reactivity in these tumors. RESULTS: Of the 12 cases 9 were columnar/mucinous adenocarcinoma, 2 clear cell adenocarcinoma and 1 a cribriform pattern resembling adenocarcinoma of the prostate. All columnar/mucinous adenocarcinomas reacted positively (6 strongly and 3 focally) with the mAbDas1 antibody but did not react with the PSA antibody. The tumor with a cribriform pattern reacted strongly with PSA but did not react with mAbDas1. The 2 clear cell adenocarcinomas did not react with either antibody. The benign urethral specimens demonstrated strong reactivity to the mAbDas1 antibody in areas of urethritis glandularis but normal and inflamed urethral mucosa and transitional cell carcinoma did not react. CONCLUSIONS: Primary adenocarcinoma of the female urethra arises from more than 1 tissue of origin. Columnar/mucinous adenocarcinomas of the female urethra and urethritis glandularis demonstrate consistent reactivity with the mAbDas1 antibody, suggesting that these tumors arise from glandular metaplasia analogous to the potential histogenesis previously demonstrated in the bladder. PSA reactivity occurred in 1 tumor with a cribriform pattern and likely represents origin from Skene's glands. Clear cell adenocarcinomas did not react with either antibody, suggesting a third possible pathway in the development of this rare subset of adenocarcinomas.

Adenocarcinoma↗

Behçet's syndrome with left ventricular aneurysm and ruptured renal artery pseudoaneurysm.

A 21-year-old man with Behçet's syndrome presented with both a left ventricular aneurysm and a left renal artery pseudoaneurysm. After successful embolization of the ruptured pseudoaneurysm, the patient underwent successful repair of the left ventricular aneurysm. Although multiple aneurysms have been reported previously, we believe this to be the first reported case of both a ventricular aneurysm and a renal artery pseudoaneurysm afflicting a patient with Behçet's syndrome.

Adult↗

Stamey needle passage of fascial pubovaginal sling after failed vesicourethropexy.

In cases of recurrent stress urinary incontinence after failed anti-incontinence surgery, it is common for the bladder neck and anterior urethra to be fixed to the symphysis pubis, increasing the risk of inadvertent bladder perforation during reoperation. We describe a modification to the popular pubovaginal sling using a 15 degrees angled Stamey suspension needle for retropubic sling passage for the previously operated patient undergoing pubovaginal sling.

Female↗