The SPRY domain-containing SOCS box protein 1 (SSB-1) interacts with MET and enhances the hepatocyte growth factor-induced Erk-Elk-1-serum response element pathway.

The suppressor of cytokine signaling (SOCS) protein family includes a SPRY (repeats in splA and RyR) domain-containing SOCS box protein (SSB) subfamily, which consists of four members, SSB-1, SSB-2, SSB-3, and SSB-4. These proteins contain a central SPRY domain and a C-terminal SOCS box. Although some of the SOCS protein subfamilies function as adaptors for a large family of ubiquitin-protein isopeptide ligases to regulate certain signaling pathways, the function of the SSB subfamily remains to be determined.

Androgen deprivation therapy for prostate cancer: current status and future prospects.

Androgens play a major role in promoting the development and progression of prostate cancer. As a result, androgen ablation or blockade of androgen action through the androgen receptor (AR) has been the cornerstone of treatment of advanced prostate cancer. Different strategies involving this hormonal therapy produce a significant clinical response in most of the patients, but most responders eventually lose dependency, resulting in mortality.

Uroflow in murine urethritis.

Objectives: To develop a noninvasive method to measure urinary flow rate in the mouse. This could be useful for the study of bladder outlet obstruction, as well as processes affecting detrusor function in the awake animal. Genetically engineered mice can improve our understanding of a variety of human bladder diseases.

Testicular microlithiasis: a review and its association with testicular cancer.

Testicular microlithiasis (TM) is an entity of unknown etiology that results in the formation of intratubular calcifications. It is of concern to the urologist because of its possible association with intratubular germ cell neoplasia and testicular germ cell cancer. Although commonly present in patients with germ cell tumors, there appears to be no definitive association with TM and cancer.

Early versus late hormonal therapy for prostate cancer.

Hormonal therapy remains the critical therapeutic option for men with advanced prostate cancer. However, considerable uncertainty remains regarding the appropriate choice/timing and actual benefits of hormonal therapy in various situations. This article reviews the relevant studies of immediate versus deferred hormonal therapy in patients with prostate cancer.

Gender, racial and age differences in bladder cancer incidence and mortality.

Bladder cancer is the fourth most commonly diagnosed cancer in men and the eighth most common in women in the United States. While clinicians who diagnose and treat the disease recognize that bladder cancer has a unique demographic profile, the influence of such factors as age, gender and race on incidence, prognosis, and survival of patients is poorly understood, and has not been the subject of intense investigation. Both through analysis of the population-based databases of bladder cancer in the United States and Europe, as well as epidemiological studies, some of the effects of gender, race and age on this disease have begun to be explained.

Interstitial cystitis antiproliferative factor (APF) as a cell-cycle modulator.

Background: Interstitial cystitis (IC) is a chronic bladder disorder of unknown etiology. Antiproliferative factor (APF), a peptide found in the urine of IC patients, has previously been shown to decrease incorporation of thymidine by normal bladder epithelial cells. This study was performed to determine the effect of APF on the cell cycle of bladder epithelial cells so as to better understand its antiproliferative activity.

DBCCR1 mediates death in cultured bladder tumor cells.

Chromosome 9, which is often partially or fully reduced to homozygosity in bladder cancer cells, harbors several tumor suppressor loci including deleted in bladder cancer chromosome region 1 (DBCCR1) at 9q32-33. To study DBCCR1 function, stable cell lines, inducible for DBCCR1 expression by tetracycline, were made, but the DBCCR1 protein was not expressed at detectable levels. To understand the fate of DBCCR1-expressing cells, human bladder tumor cells were transiently transfected with an expression vector containing DBCCR1 fused to enhanced green fluorescent protein (EGFP).

Is there a favorable subset of patients with prostate cancer who develop oligometastases?

Objective: To analyze, retrospectively, the patterns and behavior of metastatic lesions in prostate cancer patients treated with external beam radiotherapy and to investigate whether patients with < or =5 lesions had an improved outcome relative to patients with >5 lesions.

Methods And Materials: The treatment and outcome of 369 eligible patients with Stage T1-T3aN0-NXM0 prostate cancer were analyzed during a minimal 10-year follow-up period. All patients were treated with curative intent to a mean dose of 65 Gy.

A novel MET-interacting protein shares high sequence similarity with RanBPM, but fails to stimulate MET-induced Ras/Erk signaling.

MET is a receptor protein tyrosine kinase for hepatocyte growth factor, a multifunctional cytokine controlling cell growth, morphogenesis, and motility. In our previous study, RanBPM/RanBP9, whose name originated from its ability to interact with Ran, was identified as a MET-interacting protein. RanBPM/RanBP9 activates the Ras/Erk signaling pathway by serving as an adaptor protein of MET to recruit Sos.

Follow-up of conservatively managed prostate cancer: watchful waiting and primary hormonal therapy.

Many men with newly diagnosed prostate cancer choose not to undergo curative treatment, including patients who cannot be helped by local curative therapies (especially those with metastatic disease) and patients with clinically localized disease who opt for expectant management or noncurative treatments such as androgen ablation. This article reviews the selection of patients for these noncurative approaches, strategies for clinical monitoring, the choices of intervention therapies upon progression, and when to start these therapies.

The timing of hormone therapy for men with asymptomatic advanced prostate cancer.

The most appropriate time to introduce hormonal therapy for patients with advanced prostate cancer is a contentious issue. Recent prospective studies comparing immediate and deferred hormonal therapy (medical or surgical castration) on survival outcome are reviewed with the aim of redefining the most appropriate time to initiate hormonal therapy for individual patients. The evidence supports the use of immediate hormonal therapy in previously untreated patients with advanced disease (M1) and also the use of adjuvant hormonal therapy after radical prostatectomy and lymphadenectomy for node-positive (but clinically localized) disease.

Inducible expression of catalytically active type 1 serine/threonine protein phosphatase in a human carcinoma cell line.

BACKGROUND: One of the major cellular serine/threonine protein phosphatases is protein phosphatase type 1 (PP1). Studies employing many eukaryotic systems all point to a crucial role for PP1 activity in controlling cell cycle progression. One physiological substrate for PP1 appears to be the product of the retinoblastoma susceptibility gene (pRB), a demonstrated tumor suppressor.

A pilot clinical trial of oral pentosan polysulfate and oral hydroxyzine in patients with interstitial cystitis.

Purpose: This pilot study was designed to evaluate the feasibility of a multicenter, randomized, clinical trial in interstitial cystitis (IC). Secondary objectives were to evaluate the safety and efficacy of oral pentosan polysulfate sodium (PPS), hydroxyzine, and the combination to consider their use in a larger randomized clinical trial.

Materials And Methods: A 2 x 2 factorial study design was used to evaluate PPS and hydroxyzine.

Identification of the RNA polymerase II subunit hsRPB7 as a novel target of the von Hippel-Lindau protein.

Inactivation of the von Hippel-Lindau (VHL) tumor suppressor gene is linked to the hereditary VHL disease and sporadic clear cell renal cell carcinomas (CCRCC). VHL-associated tumors are highly vascularized, a characteristic associated with overproduction of vascular endothelial growth factor (VEGF). The VHL protein (pVHL) is a component of the ubiquitin ligase E3 complex, targeting substrate proteins for ubiquitylation and subsequent proteasomic degradation.

Overproduction of vascular endothelial growth factor related to von Hippel-Lindau tumor suppressor gene mutations and hypoxia-inducible factor-1 alpha expression in renal cell carcinomas.

Unlabelled: PURPOSE The von Hippel-Lindau (VHL) tumor suppressor gene is frequently inactivated in the common type of sporadic clear cell renal cell carcinoma (RCC) as well as RCCs associated with VHL disease. The VHL protein targets hypoxia-inducible factor-1 alpha (HIF-1 alpha), a transcription factor that can induce vascular endothelial growth factor (VEGF) expression, for ubiquitination and degradation. Accumulation of HIF-1 alpha caused by mutant VHL protein in tumor cells may result in VEGF over expression, which has been used to explain the increased vascularity of RCC.

Grade progression and regression in recurrent urothelial cancer.

Purpose: Recurrent urothelial cancers are reported to have characteristics similar to those of the primary tumor, with 10% to 25% of low grade tumors recurring as high grade disease. We determined how often grade progression and regression occur and whether abnormalities in p53 protein expression in original tumors are preserved in recurrences.

Materials And Methods: Two groups of patients treated for recurrent stages Ta/T1 urothelial bladder cancers with at least 1 tumor-free examination between the index and recurrent tumors were reviewed.

Automatic localization of implanted seeds from post-implant CT images.

An automatic localization method of implanted seeds from a series of post-implant computed tomography (CT) images is described in this paper. Post-implant CT studies were obtained for patients who underwent prostate brachytherapy. Bright areas were segmented using binary thresholding in each CT slice, and geometrical information on these areas was collected.

The VHL protein recruits a novel KRAB-A domain protein to repress HIF-1alpha transcriptional activity.

The von Hippel-Lindau tumor suppressor (pVHL) is a component of an E3 ubiquitin ligase and targets hypoxia-inducible factor-1alpha (HIF-1alpha) for ubiquitylation and degradation under normoxic conditions. pVHL also directly inhibits HIF-1alpha transactivation by recruiting histone deacetylases. Here, we report a novel pVHL-interacting protein that functions as a negative regulator of HIF-1alpha transactivation.

Phase III study of interferon alfa-NL as adjuvant treatment for resectable renal cell carcinoma: an Eastern Cooperative Oncology Group/Intergroup trial.

Purpose: To evaluate the role of adjuvant interferon alfa after complete resection of locally extensive renal cell carcinoma.

Patients And Methods: A total of 283 eligible patients with pT3-4a and/or node-positive disease were randomly assigned after radical nephrectomy and lymphadenectomy to observation or to interferon alfa-NL (Wellferon, Burroughs-Wellcome, Research Park, NC) given daily for 5 days every 3 weeks for up to 12 cycles. Patients were stratified on the basis of pathologic stage.

Increased expression of the acid sphingomyelinase-like protein ASML3a in bladder tumors.

Purpose: The function of the tumor suppressor gene DBCCR1 (deleted in bladder cancer chromosome region 1) is unknown despite data supporting an important role for DBCCR1 in bladder tumorigenesis. DBCCR1 has not yet been placed in a protein family or functional pathway. Protein-protein interactions are crucial for almost every aspect of cellular function.

Activation of mitogen-activated protein kinase pathway by the antiandrogen hydroxyflutamide in androgen receptor-negative prostate cancer cells.

Whereas hydroxyflutamide (HF) has been used as an antiandrogen to block androgen-stimulated prostate tumor growth, the antiandrogen withdrawal syndrome that allows antiandrogens to stimulate prostate tumor growth still occurs in many patients treated with androgen ablation therapy. This was previously explained by mutations in the androgen receptor (AR) and/or modulation from AR coregulators, so that HF becomes an AR agonist. Using immunohistochemical analysis, we analyzed four prostate cancer patients undergoing androgen ablation therapy with flutamide and compared their phospho-extracellular signal-regulated kinase 1/2 levels in prostate cancer biopsies before receiving HF and after experiencing disease progression while taking HF.

CT in detecting urinary tract calculi: influence on patient imaging and clinical outcomes.

Purpose: To determine changes in examination patterns and effectiveness of care since the introduction of unenhanced helical computed tomography (CT) for examination of patients presenting to the emergency department (ED) with symptoms of urinary tract calculi (UTC).

Materials And Methods: Hospital clinical and radiology information systems were used to retrospectively identify patients presenting with UTC symptoms from January to December 1997 (before introduction of unenhanced CT) and from January to December 1999 (after introduction of unenhanced CT). Chart abstraction was used to confirm the identification of patients with presenting symptoms suggestive of UTC and assess patient outcomes.

Continuous bladder infusion methods for studying voiding function in the ambulatory mouse.

Objectives: To develop a method for chronic cannulation of the mouse bladder that would enable repeated intravesical drug delivery and measurement of voiding patterns in unrestrained mice under controlled infusion conditions.

Methods: Fifteen female mice were anesthetized with halothane and implanted with a 3F polyurethane bladder catheter. The catheter exited from the back through mesh and a polysulfone button into a spring coil that protected the catheter and tethered the mouse.