Matrix metalloproteinase and heparin-stimulated serine proteinase activities in post-prostate massage urine of men with prostate cancer.

Proteinases secreted by the prostate gland have a reproductive function in cleaving proteins in the ejaculate and in the female reproductive tract, but some may have a fundamental role in disease and pathological processes including cancer. The purpose of this study was to determine if there were differences in proteinase activities in urine samples collected following prostate massage of men positive (CaP) or negative (no evidence of malignancy, NEM) for biopsy determined prostate cancer. Matrix metalloproteinase (MMP) and serine proteinase activities were detected using protein substrate zymography.

Tenfibgen ligand nanoencapsulation delivers bi-functional anti-CK2 RNAi oligomer to key sites for prostate cancer targeting using human xenograft tumors in mice.

Protected and specific delivery of nucleic acids to malignant cells remains a highly desirable approach for cancer therapy. Here we present data on the physical and chemical characteristics, mechanism of action, and pilot therapeutic efficacy of a tenfibgen (TBG)-shell nanocapsule technology for tumor-directed delivery of single stranded DNA/RNA chimeric oligomers targeting CK2αα' to xenograft tumors in mice. The sub-50 nm size TBG nanocapsule (s50-TBG) is a slightly negatively charged, uniform particle of 15 - 20 nm size which confers protection to the nucleic acid cargo.

Alvimopan accelerates gastrointestinal recovery after radical cystectomy: a multicenter randomized placebo-controlled trial.

Background: Radical cystectomy (RC) for bladder cancer is frequently associated with delayed gastrointestinal (GI) recovery that prolongs hospital length of stay (LOS).

Objective: To assess the efficacy of alvimopan to accelerate GI recovery after RC.

Design, Setting, And Participants: We conducted a randomized double-blind placebo-controlled trial in patients undergoing RC and receiving postoperative intravenous patient-controlled opioid analgesics.

Alvimopan, a peripherally acting μ-opioid receptor antagonist, is associated with reduced costs after radical cystectomy: economic analysis of a phase 4 randomized, controlled trial.

Purpose: We evaluated the effect of alvimopan treatment vs placebo on health care utilization and costs related to gastrointestinal recovery in patients treated with radical cystectomy in a randomized, phase 4 clinical trial.

Materials And Methods: Resource utilization data were prospectively collected and evaluated by cost consequence analysis. Hospital costs were estimated from 2012 Medicare reimbursement rates and medication wholesale acquisition costs.

Polysaccharide-K augments docetaxel-induced tumor suppression and antitumor immune response in an immunocompetent murine model of human prostate cancer.

Advanced castration-resistant prostate cancer has high mortality rates and limited treatment options. Novel therapies are needed to better contend with this disease. Polysaccharide-K® (PSK), an extract of the mushroom Trametes versicolor, has immunomodulatory and tumor suppressive activities.

Systemic administration of antisense oligonucleotides simultaneously targeting CK2α and α' subunits reduces orthotopic xenograft prostate tumors in mice.

CK2 is a highly conserved, ubiquitous, signal responsive protein serine/threonine kinase. CK2 promotes cell proliferation and suppresses apoptosis, and increased CK2 expression is observed in all cancers examined. We previously reported that direct injection of antisense (AS) CK2α phosphorothioate oligonucleotides (PTO) into xenograft prostate tumors in mice significantly reduced tumor size.

Role for toll-like receptor 4 in TNF-alpha secretion by murine macrophages in response to polysaccharide Krestin, a Trametes versicolor mushroom extract.

Woody fungi and yeast preparations show promise in cancer treatment by activating anti-tumor immune responses. Macrophages (J774A.1) were treated with PSK, Reishi extract, scleroglucan or vehicle control.

Association between lymph node density and disease specific survival in patients with penile cancer.

Purpose: We assessed the value of lymph node density for predicting disease specific survival after lymphadenectomy for penile cancer.

Materials And Methods: Data were collected retrospectively in 75 and prospectively in 88 consecutive patients with squamous cell carcinoma of the penis treated at M. D.

Increased aggressiveness of human prostate PC-3 tumor cells expressing cell surface localized membrane type-1 matrix metalloproteinase (MT1-MMP).

Membrane type-1 matrix metalloproteinase (MT1-MMP) is a multidomain transmembrane endopeptidase with a major role in physiological and pathological processes through proteolysis of extracellular matrix and other pericellular proteins. We examined cell surface function of MT1-MMP in PC-3 human prostate tumor cells selected for metastasis in nude mice (PC-3-LN4), or transfected with the full-length wild-type (WT) MT1-MMP or with the mutant form lacking the cytoplasmic tail (Delta C-MT1-MMP). Enhanced cell surface MT1-MMP was determined by fluorescence-activated cell sorting analysis and evidenced mechanistically by increased activation of proMMP-2 and invasion into type-I collagen gels.

WL-276, an antagonist against Bcl-2 proteins, overcomes drug resistance and suppresses prostate tumor growth.

Patients with hormone-refractory prostate cancer (HRPC) have an estimated median survival of only 10 months because of acquired drug resistance, urging the need to develop therapies against the drug-resistant HRPC phenotype. Accumulating evidence suggests that overexpressing antiapoptotic Bcl-2 family proteins is at least partially responsible for the development of drug resistance among HRPC patients. Antagonizing the antiapoptotic Bcl-2 family proteins, therefore, is one potential approach to circumventing drug resistance in HRPC.

Effects of soy protein isolate consumption on prostate cancer biomarkers in men with HGPIN, ASAP, and low-grade prostate cancer.

Fifty-eight men at high risk of prostate cancer or with low-grade prostate cancer were randomly assigned to consume 1 of 3 protein isolates containing 40 g protein: 1) soy protein (SPI+, 107 mg isoflavones/d); 2) alcohol-washed soy protein (SPI-, <6 mg isoflavones/d); or 3) milk protein (MPI). Proliferating cell nuclear antigen (PCNA), epidermal growth factor receptor, B-cell non-Hodgkin lymphoma-2 (Bcl-2), and Bcl-2-associated X protein (Bax) were assessed in baseline and ending prostate biopsy cores. Serum collected at 0, 3, and 6 mo was analyzed for total and free prostate specific antigen (PSA).

Soy protein isolate increases urinary estrogens and the ratio of 2:16alpha-hydroxyestrone in men at high risk of prostate cancer.

Specific estrogen metabolites may initiate and promote hormone-related cancers. In epidemiological studies, significantly lower excretion of urinary estradiol (E2) and lower ratio of urinary 2-hydroxy estrogens to 16alpha-hydroxyestrone (2:16 OH-E1) have been reported in prostate cancer cases compared to controls. Although soy supplementation has been shown to increase the ratio 2:16 OH-E1 in women, no studies to our knowledge have investigated the effects of soy supplementation on estrogen metabolism in men.

Isoflavone-rich soy protein isolate suppresses androgen receptor expression without altering estrogen receptor-beta expression or serum hormonal profiles in men at high risk of prostate cancer.

The purpose of this study was to determine the effects of soy protein isolate consumption on circulating hormone profiles and hormone receptor expression patterns in men at high risk for developing advanced prostate cancer. Fifty-eight men were randomly assigned to consume 1 of 3 protein isolates containing 40 g/d protein: 1) soy protein isolate (SPI+) (107 mg/d isoflavones); 2) alcohol-washed soy protein isolate (SPI-) (<6 mg/d isoflavones); or 3) milk protein isolate (0 mg/d isoflavones). For 6 mo, the men consumed the protein isolates in divided doses twice daily as a partial meal replacement.

CK2 signaling in androgen-dependent and -independent prostate cancer.

Protein serine/threonine kinase casein kinase 2 (CK2) is a key player in cell growth and proliferation but is also a potent suppressor of apoptosis. CK2 has been found to be dysregulated in all the cancers that have been examined, including prostate cancer. Investigations of CK2 signaling in the prostate were originally initiated in this laboratory, and these studies have identified significant functional activities of CK2 in relation to normal prostate growth and to the pathobiology of androgen-dependent and -independent prostate cancer.

Risk factors for upper tract recurrence in patients undergoing long-term surveillance for stage ta bladder cancer.

Purpose: While the evidence is clear that patients with carcinoma in situ or high grade T1 TCC of the bladder are at higher risk for developing UUT tumors, the role of imaging the UUT in patients with Ta tumors remains controversial. We hypothesized that the number and frequency of recurrences in patients with Ta disease would allow us to identify a population who should undergo routine UUT surveillance.

Materials And Methods: We reviewed our database of 375 patients who underwent resection of a stage Ta TCC between 1975 and 1995.

Downregulation of CK2 induces apoptosis in cancer cells--a potential approach to cancer therapy.

We have previously documented that naked antisense CK2alpha ODN can potently induce apoptosis in cancer cells in culture and in mouse xenograft human prostate cancer. The effects of the antisense CK2alpha are related to downregulation of CK2alpha message and rapid loss of the CK2 from the nuclear compartment. Here we demonstrate that downregulation of CK2 elicited by diverse methods leads to inhibition of cell growth and induction of apoptosis.

Elevation of dipeptidylpeptidase iv activities in the prostate peripheral zone and prostatic secretions of men with prostate cancer: possible prostate cancer disease marker.

Purpose: Dipeptidylpeptidase IV (DPIV) is a multifunctional type II plasma membrane glycoprotein with serine-type exopeptidase activity that is secreted by the prostate and increased in prostate cancer. We determined whether changes in DPIV activities in prostatic tissue zones and expressed secretions were associated with the presence of cancer.

Materials And Methods: Expressed prostatic secretion (EPS), and biopsy of the transition (TZ) and peripheral (PZ) zones were collected from men undergoing ultrasound guided prostate biopsy.

Induction of apoptosis by antisense CK2 in human prostate cancer xenograft model.

Protein serine/threonine kinase CK2 (formerly casein kinase 2) is a ubiquitous protein kinase that plays key roles in cell growth, proliferation, and survival. We have shown previously that its molecular down-regulation induces apoptosis in cancer cells in culture. Here, we have employed a xenograft model of prostate cancer to extend these studies to determine whether antisense CK2alpha evokes a similar response in vivo.

Percutaneous renal stone extraction: in vitro study of retrieval devices.

Purpose: Traditionally, percutaneous stone extraction has relied on the use of 2-prong and 3-prong graspers, which are prone to causing trauma to the urothelium. We evaluate the efficiency of stone removal with a novel tipless stone basket designed specifically for percutaneous procedures.

Materials And Methods: A 3, 5 and 8 mm human calculus were placed in the calix of a percutaneous renal model.

Tumor length and location of cancer on biopsy predict for side specific extraprostatic cancer extension.

Purpose: We studied preoperative variables in a contemporary series of men who underwent nonnerve sparing radical prostatectomy in an effort to establish criteria that would predict side specific extraprostatic extension (EPE) of cancer.

Materials And Methods: We reviewed the records of 430 patients who underwent radical prostatectomy for localized prostate cancer with no prior therapy between 1996 and 1998, and for whom we had at least sextant biopsy information. We evaluated biopsy data (Gleason score, maximum length of cancer in positive cores, percent of cancer per involved core, proportion of positive biopsy cores, tumor location and number of positive biopsy cores) and correlated these findings with EPE at the neurovascular bundle and posterior lateral (NVB/PL) region.

Prognostic value of body mass index in patients undergoing nephrectomy for localized renal tumors.

Objectives: To identify whether the body mass index (BMI) has any adverse effect on the prognosis of patients with established renal cell carcinoma, given the increasing prevalence of obesity and the rising incidence of renal cell carcinoma in the United States.

Methods: We reviewed the records of patients who underwent nephrectomy for localized disease between 1985 and 1998 at our institution. Patients were grouped according to BMI as normal (less than 25 kg/m2), overweight (25 to 30 kg/m2), or obese (more than 30 kg/m2).

Correlation of metastasis related gene expression and relapse-free survival in patients with locally advanced bladder cancer treated with cystectomy and chemotherapy.

Purpose: Patients with locally advanced (ie clinically extravesical) transitional cell carcinoma are at high risk for recurrence after cystectomy. Although randomized trials have established an incremental benefit from the addition of chemotherapy in this setting, many patients still have disease relapse, and therefore it is necessary to determine patient and tumor characteristics that correlate with outcome in this setting. We investigated the tumor expression of several metastasis related genes and the association of gene expression with disease specific survival of patients with locally advanced transitional cell carcinoma treated randomized to either neoadjuvant or adjuvant chemotherapy and radical cystectomy.

Surgical management of renal cell carcinoma associated with complex inferior vena caval thrombi.

The operative morbidity and mortality of radical nephrectomy are considerably higher when the vena cava is involved by the tumor. The prognostic significance of vena caval extension in this setting remains controversial. We reviewed our experience of vena caval thrombectomy specifically addressing prognostic factors.

Clinical presentation and outcome of high-grade urinary bladder leiomyosarcoma in adults.

Objectives: To determine the clinical presentation and outcome of patients with high-grade bladder leiomyosarcoma.

Methods: Between July 1986 and April 1998, 36 adult patients (mean follow-up 56 months) with a diagnosis of urinary bladder leiomyosarcoma were evaluated at the University of Texas M. D.

Repeated intravesical instillations of an adenoviral vector in patients with locally advanced bladder cancer: a phase I study of p53 gene therapy.

Purpose: We investigated the feasibility, safety, and biologic activity of adenovirus-mediated p53 gene transfer in patients with locally advanced bladder cancer.

Patients And Methods: Patients with measurable, locally advanced transitional-cell carcinoma of the bladder who were not candidates for cystectomy were eligible. On a 28-day cycle, intravesical instillations of INGN 201 (Ad5CMV-p53) were administered on days 1 and 4 at three dose levels (10(10) particles to 10(12) particles) or on either 4 or 8 consecutive days at a single dose level (10(12) particles).