Angiogenin promotes tumoral growth and angiogenesis by regulating matrix metallopeptidase-2 expression via the ERK1/2 pathway.

Tumor angiogenesis is essential for tumor growth and metastasis and is dependent on key angiogenic factors. Angiogenin (ANG), a 14.2-kDa polypeptide member of the RNase A superfamily, is an angiogenic protein that has been reported to be upregulated and associated with poor prognosis in some human cancers. The mechanisms through which aberrant ANG levels promote specific steps in tumor progression are unknown. Here, we show that ANG expression in human tissues is strongly correlated with an invasive cancer phenotype. We also show that ANG induces cellular survival, proliferation, endothelial tube formation and xenograft angiogenesis and growth. Novel mechanistic investigations revealed that ANG expression stimulated matrix metallopeptidase-2 (MMP2) expression through the phosphorylation of ERK1/2. Targeting ANG in vivo with N65828, a small-molecule inhibitor of the ribonucleolytic activity of human ANG, resulted in the diminution of xenograft tumoral growth through the inhibition of angiogenesis. Our findings support an unrecognized interplay between ANG, ERK1/2 and MMP2 that can impact tumor growth and progression. The targeting of ANG and associated factors could provide a novel strategy to inhibit tumor establishment and growth.

Molecular diagnostic trends in urological cancer: biomarkers for non-invasive diagnosis.

The early detection of urological cancers is pivotal for successful patient treatment and management. The development of molecular assays that can diagnose disease accurately, or that can augment current methods of evaluation, would be a significant advance. Ideally, such molecular assays would be applicable to non-invasively obtained body fluids, enabling not only diagnosis of at risk patients, but also asymptomatic screening, monitoring disease recurrence and response to treatment. The advent of advanced proteomics and genomics technologies and associated bioinformatics development is bringing these goals into focus. In this article we will discuss the promise of biomarkers in urinalysis for the detection and clinical evaluation of the major urological cancers, including bladder, kidney and prostate. The development of urine-based tests to detect urological cancers would be of tremendous benefit to both patients and the healthcare system.

Utility of serial urinalyses and urinary cytology in the evaluation of patients with microscopic haematuria.

BACKGROUND: Serial urinalyses have been advocated when haematuria is suspected. OBJECTIVE: To determine the utility of serial urinalyses and urinary cytology in patients presenting for evaluation of microscopic haematuria. METHODS: Eighty-five patients with the diagnosis of microscopic haematuria were evaluated at a tertiary-care hospital. All patients had a comprehensive urologic evaluation. Clinic and hospital records were reviewed for key factors (e.g., demographic, pathology, radiologic findings and operative findings). RESULTS: One hundred ninety total urinalyses were reviewed. Eighty-eight (46%) urinalyses were classified as normal, 87 (46%) as haematuria (> 3 RBC/hpf), and 15 (8%) as pyuria/ bacteriuria. The initial urinalysis detected haematuria in 95% of the patients. The addition of the second and third urinalyses detected haematuria in the remaining 5% of the patients with haematuria. Aetiologic factors for microscopic haematuria include urolithiasis 15 (18%), infection 9 (11%) and bladder lesion/tumor 6 (7%). In this setting of microscopic haematuria, urinary cytology was not able to detect any of the five documented bladder tumors. Fifty-seven percent of patients had a negative haematuria evaluation. CONCLUSION: In the evaluation of the patient with microscopic haematuria, serial urinalyses may have a low yield. Further prospective studies are needed to further evaluate serial urinalyses in this cohort.

Exogenous mycoplasmal p37 protein alters gene expression, growth and morphology of prostate cancer cells.

We previously showed that the Mycoplasma hyorhinis-encoded protein p37 can promote invasion of cancer cells in a dose-dependent manner, an effect that was blocked by monoclonal antibodies specific for p37. In this study, we further elucidated changes in growth, morphology and gene expression in prostate cancer cell lines when treated with exogenous p37 protein. Incubation with recombinant p37 caused significant nuclear enlargement, denoting active, anaplastic cells and increased the migratory potential of both PC-3 and DU145 cells. Microarray analysis of p37-treated and untreated cells identified eight gene expression clusters that could be broadly classified into three basic patterns. These were an increase in both cell lines, a decrease in either cell line or a cell line-specific differential trend. The most represented functional gene categories included cell cycle, signal transduction and metabolic factors. Taken together, these observations suggest that p37 potentiates the aggressiveness of prostate cancer and thus molecular events triggered by p37 maybe target for therapy.

Gene therapy for superficial bladder cancer.

In this review, the basics of gene therapy and the strategies to increase the therapeutic effect of gene therapy for superficial bladder cancer are discussed. Strategies considered in detail are modification of the structure of vectors, modification of the promoters of viral vectors and the timing and route of vector administration. Although all of these modifications have shown some degree of improvement for gene transfer, the use of polyamides intravesically in conjunction with an adenoviral system shows the most promise and the greatest potential to supplement or even replace the current treatment modalities for superficial bladder cancer.

Are coagulation studies necessary before percutaneous nephrostomy?

PURPOSE: Performance of coagulation studies for patients undergoing percutaneous nephrostomy (PCN) has been advocated by some investigators. We performed a retrospective study to assess this practice. MATERIALS AND METHODS: The medical records of 180 patients subjected to PCN for various reasons between October 1991 and July 1998 were reviewed. This represents a subset of patients in whom PCN was performed by an experienced interventional radiologist at our institution. Patients were excluded if they had a history of active liver disease, hematologic or bleeding disorder, current use of heparin or warfarin, or platelet count <100,000. The remaining 160 patients were separated into two groups. Group 1 consisted of 153 patients with a normal prothrombin time (PT) and partial thromboplastin time (PTT). Group 2 comprised 7 patients with an abnormal PT or PTT. Demographic and laboratory data including PT, PTT, complete blood, and platelet counts were analyzed to determine if a hemorrhagic complication could be predicted by an abnormal PT or PTT. RESULTS: In group 1 the mean PT was 12.2 seconds and the mean PTT was 25.0 seconds; in group 2 the mean PT was 13.9 seconds and the mean PTT was 30.3 seconds. The hemorrhagic complication rates were not statistically different between the two patient cohorts (p = .203). Demographic and standard laboratory data were not predictive of abnormal coagulation parameters. CONCLUSIONS: Screening coagulation studies are unnecessary in the standard patient subjected to PCN.

Is there a learning curve in diagnosing urolithiasis with noncontrast helical computed tomography?

OBJECTIVE: To report one department's experience with helical computed tomographic (HCT) evaluation of patients with suspected renal colic to diagnose ureteral calculi; to determine whether there is a learning curve in performing HCT in this context; and to determine whether HCT for the evaluation of renal colic exposes patients to more radiation than the standard intravenous pyelography (IVP) combined with nephrotomography. METHODS: All patients presenting to the emergency department with flank or abdominal pain were evaluated with nonreformatted noncontrast HCT. To determine changes in diagnostic accuracy, patients were divided into 2 groups: those evaluated between September 1996 and January 1997 (group 1, 67 patients), and those seen from February to June 1997 (group 2, 53 patients). A radiation exposure study was performed using phantoms, and radiation exposure for HCT, IVP and nephrotomography was measured. RESULTS: Review of HCT scans to diagnose ureteral calculi had a sensitivity of 91.7%, specificity of 82.6%, and accuracy of 87.2% in group 1, and a sensitivity of 95.5%, specificity of 86.7%, and accuracy of 91.9% in group 2. Patients undergoing IVP with nephrotomography were exposed to an effective dose equivalent of 343 mrem (dSv) (for men) and 664 mrem (for women). The effective dose equivalent for an HCT scan was 180 mrem. CONCLUSION: HCT offers excellent, rapid diagnostic accuracy without the need for intravenous contrast medium and with a lower radiation exposure level than IVP in evaluating patients with acute flank pain. There is a small but real learning curve in evaluating patients with acute flank pain with HCT.

Thoracoabdominal radical nephrectomy: is a postoperative thoracostomy tube necessary?

OBJECTIVES: To report our results of patients undergoing thoracoabdominal radical nephrectomy without intraoperative placement of a thoracostomy tube. It has been routine in our hospital to not place a thoracostomy tube in patients undergoing thoracoabdominal radical nephrectomy since 1988. METHODS: We conducted a retrospective review of 47 thoracoabdominal radical nephrectomies performed from January 1988 through November 1998 at our institution. Of the 47 patients, 39 did not have a thoracostomy tube placed intraoperatively; the other 8 patients did. The development of all postoperative complications, length of hospital stay, and hospital charges were noted. RESULTS: No postoperative mortality was noted in our study. Of the 47 patients in the study, 20 patients had a total of 29 complications. The overall number of complications was not increased in the group without a thoracostomy tube compared with the group with a thoracostomy tube (P = 0.104). No patient treated without a thoracostomy tube required subsequent placement of a tube for persistent pneumothorax. The mean length of hospital stay in patients with a thoracostomy tube after radical nephrectomy was 9.14 +/- 2.65 days; in patients without a thoracostomy tube, the mean length of stay was 7.07 +/- 3.97 days (P = 0.071). CONCLUSIONS: In patients without parietal pleural injury, thoracoabdominal radical nephrectomy without the placement of a thoracostomy tube can be performed safely and effectively, with a low risk of postoperative complications and a decrease in the overall hospital stay and hospital charges.

Metastatic small cell carcinoma to the testis.

Testicular neoplasms comprise 1% of all malignancies in men, with less than 3% of these malignancies due to metastatic disease. We report a case of a 51-year-old man with a history of left pneumonectomy done 2 years earlier for small cell carcinoma of the lung; the patient came to his primary care physician for routine follow-up. Physical examination was significant for a left testicular mass, which on final pathology was diagnosed as metastatic small cell carcinoma.

Metastatic adenocarcinoma of the pancreas to the testicle: a case report.

We report a 58-year-old man who presented with a 1-month history of left testicular pain and swelling that was eventually diagnosed as metastatic adenocarcinoma from the pancreas. Currently, there are only three accounts in the English literature of metastatic pancreatic carcinoma to the testis.

Detection of high-grade prostatic intraepithelial neoplasia with the five-region biopsy technique.

OBJECTIVES: To assess the ability of the five-region biopsy technique compared with the traditional sextant biopsy technique to detect high-grade prostatic intraepithelial neoplasia (PIN) in patients with an abnormal digital rectal examination or elevated prostate-specific antigen, or both, by a retrospective study. METHODS: We conducted a retrospective review of 50 consecutive patients diagnosed with PIN at our institution from January 1 990 to May 1998. Of the 50 patients, 26 patients were diagnosed with high-grade PIN. The reasons for the initial prostate biopsy were elevated prostate-specific antigen in 15 patients, abnormal digital rectal examination in 1 patient, and combined abnormalities in 10 patients. These patients underwent transrectal ultrasound-guided needle biopsy of the prostate using the five-region biopsy technique. Biopsy findings from regions 1, 3, and 5 (additional five-region biopsies) were compared with those of regions 2 and 4 (traditional sextant biopsies). RESULTS: Of the 26 patients, PIN was detected in the sextant regions in only 14 patients (53%). However, by using the five-region biopsy technique, an additional 1 2 patients (47%) were diagnosed with PIN (P <0.05). Twenty-four patients underwent repeated five-region biopsies. Eight (33%) of the 24 patients were found to have prostate cancer. Of the eight patients with cancer, 5 of the cancers were found with the five-region biopsy technique. CONCLUSIONS: In this study, the five-region method of prostate biopsy significantly increased the diagnosis of PIN compared with the traditional sextant method of biopsy. Furthermore, 33% of patients diagnosed with high-grade PIN on the initial biopsies were found to have prostate cancer on subsequent five-region biopsies.

Urinary tract infections in the critically ill patient with a urinary catheter.

BACKGROUND: The diagnosis of urosepsis should be entertained each time a patient has a febrile episode. Urosepsis carries with it a mortality rate of 25% to 60%. We determined the incidence and risk factors of urosepsis in the catheterized critically ill patient. MATERIALS AND METHODS: The charts of 142 subjects admitted from November 1994 to November 1995 to the trauma intensive care units at our institution with a urinary catheter were reviewed. Urosepsis was defined as (1) positive blood and urine cultures that correlated; (2) positive urine cultures with radiologic evidence of obstructive uropathy or infection; or (3) positive urine cultures and all other cultures negative to be eligible for the urosepsis group. RESULTS: Of the 126 patients evaluated for sepsis, 20 (15.8%) were diagnosed with urosepsis. Multivariant analysis demonstrated that the incidence of urosepsis was correlated with the following: age >60 years, extended length of stay in the intensive care unit and/or hospital, and duration of urinary catheterization. All 20 patients who developed urosepsis had a positive urinalysis and a positive urine culture (sensitivity 100%). However, urinalyses were positive in another 63 patients who did not have urosepsis (specificity 24.1%), and urine cultures were positive in 31 patients who did not have urosepsis (specificity 70.8%). CONCLUSION: We found a 15.8% incidence of urosepsis in our patient population. Urosepsis was more likely to occur in patients over 60 years of age, patients with extended length of stay in the intensive care unit or in the hospital in general, and patients with an extended duration of urinary catheterization.