Osteoblasts can stimulate prostate cancer growth and transcriptionally down-regulate PSA expression in cell line models.

Introduction: To investigate the effect of bone environment on cellular proliferation, mature prostate-specific antigen (PSA) production and secretion, and PSA transcriptional regulation of prostate cancer cells.

Materials And Methods: Androgen-independent C4-2 prostate cancer cells were co-cultured with various osteoblastic cells in a transwell system. Proliferation was measured via cell counting and MTT assay.

Telomerase enzyme inhibition (TEI) and cytolytic therapy in the management of androgen independent osseous metastatic prostate cancer.

Background: Recurrent prostate cancer can be osseous, androgen independent and lethal. The purpose is to discern the efficacy of synthetic small molecule telomerase enzyme inhibitors (TEI) alone or in combination with other cytotoxic therapies in controlling metastatic osseous prostate cancer.

Methods: C4-2B was pre-treated with a match or mismatch TEI for 6 weeks and then inoculated into nude mice subcutaneously or intraosseously.

Conditionally replicating adenovirus therapy utilizing bone sialoprotein promoter (Ad-BSP-E1a) in an in vivo study of treating androgen-independent intraosseous prostate cancer.

Background: Adenoviral based gene therapy has been used in clinical trials in control of advanced prostate cancer. In this study, a promising conditionally replicating adenovirus (CRAd) driven by a tissue specific bone sialoprotein promoter in controlling prostate cancer both in vitro and in vivo is demonstrated.

Methods: C4-2B, an androgen-independent prostate cancer cell line, was treated with PBS, Ad-BSP-TK, or the Ad-BSP-E1a in vitro, and in subcutaneous and intraosseous xenographs.

Robotic surgical education: a collaborative approach to training postgraduate urologists and endourology fellows.

Objective: Currently, robotic training for inexperienced, practicing surgeons is primarily done vis-à-vis industry and/or society-sponsored day or weekend courses, with limited proctorship opportunities. The objective of this study was to assess the impact of an extended-proctorship program at up to 32 months of follow-up.

Methods: An extended-proctorship program for robotic-assisted laparoscopic radical prostatectomy was established at our institution.

Local-regional prostate cancer.

Historically, locally advanced prostate cancer was defined clinically with the digital rectal exam (DRE). With the introduction of screening prostate specific antigen (PSA), further pretreatment stratification of locally advanced prostate cancer was possible. Tables and nomograms have been developed to predict pathologic staging prior to therapy.

Prostate cancer disease-free survival after radical retropubic prostatectomy in patients older than 70 years compared to younger cohorts.

Objectives: To evaluate the feasibility of radical retropubic prostatectomy (RRP) as an option for treating men older than 70 years with organ confined prostate cancer and to compare biochemical progression-free survival with younger cohorts.

Materials And Methods: A total of 689 consecutive patients who were treated with RRP from 1994 to 2002 for clinically localized prostate cancer were categorized into 3 different age groups: younger than 50 years (n = 49), 50-70 years (n = 601), and older than 70 years (n = 39). Patients older than 70 years were healthy individuals for their age.

Conditionally replicating adenovirus-mediated gene therapy in bladder cancer: an orthotopic in vivo model.

Introduction: The effects of a conditionally replicating adenovirus on various bladder cancer lines were explored, a truncated bone sialoprotein (BSP) promoter controlling the E1a/b lytic-regulating sequence was used, since BSP protein is found in many osteotropic neoplasms, including bladder cancer.

Methods: Reverse transcriptase polymerase chain reaction analysis was used to determine expression patterns of BSP and Coxsackie adenovirus receptor, a receptor known to interact with adenovirus, on multiple lines of bladder cancer (253J, 253J B-V, RT4, transitional cell carcinoma, T24, UMUC3, and WH). Ad-BSP-E1a was tested in vitro for lytic activity on 4 of these cell lines.

Bladder cancer: toward state of the art multidisciplinary molecular medicine.

Recent advances in bladder cancer research, and clinical diagnosis and therapy are explored. Major advances in biologic understanding are applied toward better early diagnosis and staging. Using molecular medicine to help informed clinical trial design and implementation will lead to more effective therapeutic intervention in transitional cell carcinoma.

Synthesis and evaluation of a novel gene reporter molecule: detection of beta-galactosidase activity using 19F NMR of a fluorinated vitamin B6 conjugate+.

Gene therapy has emerged as a promising strategy for treatment of various diseases. However, widespread implementation is hampered by difficulties in assessing the success of transfection, in particular, the spatial extent of expression in the target tissue and the longevity of expression. Thus, the development of non-invasive reporter techniques based on appropriate molecules and imaging modalities may help to assay gene expression.

Small molecule, oligonucleotide-based telomerase template inhibition in combination with cytolytic therapy in an in vitro androgen-independent prostate cancer model.

Purpose: Determine the efficacy and timing of small molecule oligonucleotide-based inhibitors to the enzyme telomerase in an in vitro model of androgen-independent, osseous prostate cancer.

Materials And Methods: Telomerase was inhibited in prostate cancer cell lines C4-2/C4-2B and in controls by using small molecule antisense oligonucleotide-based inhibitors alone or in various combinations of small-dose Taxotere (sanofi-aventis, Bridgewater, NJ) and/or conditionally replication competent adenovirus (AD-BSP-E1a). After transfection and proliferation, telomerase telomeric repeat amplification protocol and telomere restriction fragment assays were performed, with specific times for evaluating telomere length.

Prostate cancer stem cells, telomerase biology, epigenetic modifiers, and molecular systemic therapy for the androgen-independent lethal phenotype.

Numerous, relatively well-characterized androgen-independent osteotropic prostate cancer cell lines are now available to interrogate clinically relevant fundamental questions of prostate cancer metastasis and lethal progression systematically. Mounting basic and translational science efforts reveal that, very likely, the currently incurable form of androgen independent osseous prostate cancer originates from a more undifferentiated or "stem cell" like component, coexisting within a heterogeneous tumor mass containing more differentiated epithelial cancer subtypes. Current therapeutic preclinical investigations point toward the use of epigenetic modifiers, such as histone deacetylase inhibitors, to abrogate the continued survival of prostate cancer cells and likely can be used relatively chronically, with little morbidity.

Strategies for targeted tumor assessment and elimination: the physician-scientist and the blossoming of molecular medicine in urologic oncology.

To realize its full potential in treating urologic malignancies, molecular medicine in the post-genomic era requires the science of molecular biology to become a great force of change directed to the critical health questions confronting the clinician. The clinician-scientist is the linchpin to convert an exploratory, reactive stance to a predictive and efficacious paradigm in treating urologic malignancies. The explosion of basic and translational discoveries will demand a "systems biology" approach at the fingertips of the future clinician, and realize the dream of proactive and highly adaptable "engineered" response to the very complex "survival" biology of urologic tumors.

Elevated activated partial thromboplastin time during administration of first-generation adenoviral vectors for gene therapy for prostate cancer: identification of lupus anticoagulants.

Objectives: To evaluate the cause and significance of elevated activated partial thromboplastin time (aPTT) in a group of patients who received a first-generation adenoviral vector (Ad-OC-TK) delivering a toxic gene to prostate cancer cells as part of a Phase I clinical trial at the University of Virginia.

Methods: Eleven subjects were injected intratumorally to metastatic lesions of prostate cancer in the prostatic fossa, retroperitoneal lymph nodes, or bone (iliac, ischium, or vertebrae). After the initial laboratory evaluation, patients with elevated aPTT underwent a series of additional tests, including mixing studies, coagulation factor, prekallikrein, and high-molecular-weight kininogen, and lupus anticoagulant studies (modified Russell viper venom time) with phospholipid correction, and a Staclot LA assay.

Hand-assisted laparoscopic nephrectomy for renal masses >9.5 cm: series comparison with open radical nephrectomy.

Objective: To assess the feasibility of hand-assisted laparoscopic nephrectomy (HALN) for large renal masses (stage T2, mean size 9.7 cm) and compare outcomes with a similar cohort undergoing open radical nephrectomy (ORN).

Methods: A nonrandomized comparison of 19 consecutive patients who underwent nephrectomy for renal masses >or=7 cm was performed.

The utility of screening renal ultrasonography: identifying renal cell carcinoma in an elderly asymptomatic population.

Objective: To evaluate the efficacy and utility of screening renal ultrasonography (RUS) in older patients with a high prevalence of risk factors for renal cell carcinoma (RCC), as with the widespread use of advanced imaging techniques the identification of incidental RCC has increased, and although previous studies in low-risk groups reported little use for screening RUS, its utility in high-risk groups is unknown.

Patients And Methods: From 1993 to 1997, screening RUS was completed for 6678 consecutive patients in conjunction with the Aneurysm Detection and Management study. Patient demographics, medical and social history were recorded for each patient.

Hand assisted laparoscopic cystectomy with minilaparotomy ileal conduit: series report and comparison with open cystectomy.

Purpose: To achieve less patient morbidity our initial experience with hand assisted laparoscopic (HAL) cystectomy was compared with our results of open cystectomy with similar urinary diversion.

Materials And Methods: During 18 months 36 cystectomies were performed, including 20 with open continent diversion. A prospective, nonrandomized comparison of the remaining 16 consecutive cystectomies with ileal conduit diversion (hand assisted laparoscopic cystectomy and open cystectomy in 8 cases each) was performed.

Changing management of organ-confined renal masses.

Background And Purpose: Rapid evolution of laparoscopic and ablative techniques is changing the approach to renal masses. We evaluated our approach to managing renal masses in light of newly available technology.

Patients And Methods: The records for all patients who underwent treatment for a renal mass between January 2000 and July 2002 at UT Southwestern Medical Center were reviewed for patient demographics, operative details, and pathology results.

Predictive value of primary Gleason pattern 4 in patients with Gleason score 7 tumours treated with radical prostatectomy.

Objective: To examine whether Gleason score (GS) 3 + 4 and 4 + 3 cancers at radical prostatectomy behave differently and whether this behaviour is independently associated with prostate cancer outcome.

Patients And Methods: From July 1994 to December 2002 309 consecutive men who had a radical retropubic prostatectomy for clinically localized disease had final GS 7 tumours in their prostatectomy specimen. Statistical analyses, including multivariate logistic regression, were used to evaluate the association between variables, i.

The percent of biopsy cores positive for cancer is a predictor of advanced pathological stage and poor clinical outcomes in patients treated with radical prostatectomy.

Purpose: We examined if the percent of positive biopsies is associated with features of biologically aggressive prostate cancer, biochemical progression and development of distant metastases in patients undergoing radical prostatectomy (RP).

Materials And Methods: Multivariate analyses of preoperative features in 605 consecutive patients who underwent RP for clinically localized disease were evaluated to determine the association between the percent positive biopsy cores (PosBx), pathological stage and grade, and biochemical progression following RP. The percent of PosBx cores was defined using the formula, (number of positive biopsy cores/total number of biopsy cores) x 100.

Cellular interactions in the tropism of prostate cancer to bone.

At autopsy >or=80% of prostate cancers have established macrometastases in marrow containing bone. The mechanism(s) to explain this remarkable level of bone involvement remain to be elucidated. We examined the adhesive and invasive behavior of prostate cancer cells to osteoblastic and human bone marrow endothelial cells (HBME-1) in an attempt to explain the tropism of prostate cells for bone.

Novel NMR approach to assessing gene transfection: 4-fluoro-2-nitrophenyl-beta-D-galactopyranoside as a prototype reporter molecule for beta-galactosidase.

Gene therapy holds great promise for the treatment of diverse diseases. However, widespread implementation is hindered by difficulties in assessing the success of transfection in terms of spatial extent, gene expression, and longevity of expression. The development of noninvasive reporter techniques based on appropriate molecules and imaging modalities may help to assay gene expression.

Lymphovascular invasion is a pathological feature of biologically aggressive disease in patients treated with radical prostatectomy.

Unlabelled: We examined whether invasion of lymphatic and/or vascular vessels (LVI), or perineural spaces (PNI) is associated with prostate cancer features and outcome.

Materials And Methods: A total of 630 consecutive men underwent radical retropubic prostatectomy for clinically localized disease. LVI and PNI examination was part of the routine specimen evaluation.

Reassessment of the 1997 TNM classification system for renal cell carcinoma.

Background: The 1997 TNM staging classification for renal cell carcinoma (RCC) defined Stage I tumors as organ-confined tumors measuring up to 7 cm in size. The authors evaluated the validity of this cutoff size by assessing the survival of patients with Stage I RCC according to a series of alternative size cutoff values. In addition, the authors determined how these size cutoffs affected the risk of having nonorgan-confined tumors, regional lymph node involvement, and metastatic disease.