The Nuclear Guanine Nucleotide Exchange Factors Ect2 and Net1 Regulate RhoB-Mediated Cell Death after DNA Damage

Commonly used antitumor treatments, including radiation and chemotherapy, function by damaging the DNA of rapidly proliferating cells. However, resistance to these agents is a predominant clinical problem. A member of the Rho family of small GTPases, RhoB has been shown to be integral in mediating cell death after ionizing radiation (IR) or other DNA damaging agents in Ras-transformed cell lines. In addition, RhoB protein expression increases after genotoxic stress, and loss of RhoB expression causes radio- and chemotherapeutic resistance. However, the signaling pathways that govern RhoB-induced cell death after DNA damage remain enigmatic. Here, we show that RhoB activity increases in human breast and cervical cancer cell lines after treatment with DNA damaging agents. Furthermore, RhoB activity is necessary for DNA damage-induced cell death, as the stable loss of RhoB protein expression using shRNA partially protects cells and prevents the phosphorylation of c-Jun N-terminal kinases (JNKs) and the induction of the pro-apoptotic protein Bim after IR. The increase in RhoB activity after genotoxic stress is associated with increased activity of the nuclear guanine nucleotide exchange factors (GEFs), Ect2 and Net1, but not the cytoplasmic GEFs p115 RhoGEF or Vav2. Importantly, loss of Ect2 and Net1 via siRNA-mediated protein knock-down inhibited IR-induced increases in RhoB activity, reduced apoptotic signaling events, and protected cells from IR-induced cell death. Collectively, these data suggest a mechanism involving the nuclear GEFs Ect2 and Net1 for activating RhoB after genotoxic stress, thereby facilitating cell death after treatment with DNA damaging agents

Incidence of benign lesions according to tumor size in solid renal masses

Objective: The incidence of solid renal masses has increased sharply in recent years due to widespread use of abdominal imaging studies. The aim of the present study was to evaluate the incidence of benign lesions in solid renal masses according to tumor size. Materials and Methods: The authors retrospectively reviewed the records of 305 patients with 328 renal solid masses treated by surgery. Based on a report by one pathologist, the specimen tumor size and the histology of each lesion were tabulated. The frequency of renal cell carcinoma and benign renal lesions was evaluated and a correlation between tumor size and pathological features of the masses was observed. Results: The frequency of malignant lesions in the 328 renal masses was 83.2%. When lesions were stratified into groups with diameters ≤ 3 cm or > 3 cm, the incidence of benign histology was 22.9% and 13.3%, respectively (p = 0.026). The odds ratios for finding a benign lesion in masses ≤ 3 cm was 1.93 (IC 95%, 1.07 - 3.46) compared to masses > 3 cm. Conclusion: The incidence of benign lesions is significantly higher in renal masses smaller than 3 cm in diameter, which should be taken in account when the treatment of renal solid masses is planned

Retroperitoneoscopic adrenalectomy in pheochromocytoma

Since the first laparoscopic adrenalectomy, the technique has evolved and it has become the standard of care for many adrenal diseases, including pheochromocytoma. Two laparoscopic accesses to the adrenal have been developed: transperitoneal and retroperitoneal. Retroperitoneoscopic adrenalectomy may be recommended for the treatment of pheochromocytoma with the same peri-operative outcomes of the transperitoneal approach because it allows direct access to the adrenal glands without increasing the operative risks. Although technically more demanding than the transperitoneal approach, retroperitoneoscopy can shorten the mean operative time, which is critical for cases with pheochromocytoma where minimizing the potential for intra-operative hemodynamic changes is essential. Blood loss and the convalescence time can be also shortened by this approach. There is no absolute indication for either the transperitoneal or retroperitoneal approach; however, the latter procedure may be the best option for patients who have undergone previous abdominal surgery and obese patients. Also, retroperitoneoscopic adrenalectomy is a good alternative for treating cases with inherited pheochromocytomas, such as multiple endocrine neoplasia type 2A, in which the pheochromocytoma is highly prevalent and frequently occurs bilaterally

Pretreatment Tumor Volume Estimation Based on Total Serum PSA in Patients with Localized Prostate Cancer

OBJECTIVES: To establish a formula that estimates tumor volume in localized prostate cancer based on serum prostate specific antigen levels. One of the main prognostic variables in localized prostate cancer is tumor volume, which can be precisely defined only after prostate extirpation. The present study defines a simple method that allows for estimation of tumor volume before treatment, which can help to establish a better therapeutic strategy for each patient. METHODS: From 1997 to 2002, 735 patients with prostate cancer of stagesT1c-T2c without any previous treatment were submitted to radical prostatectomy. Surgical specimens were evaluated by the same pathologist and the total tumor volume (in cc) and the relative tumor volume (as the percent of the total prostate volume) were determined using the grid morphometric method. Pretreatment serum prostate specific antigen was correlated with tumor volume in each patient using a linear regression model. RESULTS: There were positive correlations between the serum levels of prostate specific antigen and the total tumor volume in cc (p<0.001) and the relative tumor volume as a percentage (p<0.001). For each ng/ml unit increment of serum prostate specific antigen, there was a 0.302 cc increase in total tumor volume and a 0.7% increase in relative tumor volume. Total and percent tumor volume could be calculated, respectively, using the formulas Volume (cc) = 3.476 + 0.302 x PSA (ng/ml) and Volume (%) = 11.331 + 0.704 x prostate specific antigen (ng/ml). CONCLUSIONS: Tumor volume in patients with prostate cancer can be determined before treatment based on the serum prostate specific antigen levels

Quimioterapia Tópica Intravesical

Cerca de 80% dos pacientes com neoplasias vesicais apresentam-se inicialmente com lesões superficiais, que têm baixa tendência à progressão e acompanham-se de prognóstico mais favorável. O comportamento menos agressivo destas lesões permite que as mesmas sejam controladas de forma relativamente segura, através da ressecção transuretral, o que elimina os inconvenientes da cistectomia radical e/ou radioterapia, indicadas em pacientes com tumores infiltrativos

Urinary tract infections

Urinary tract infections have an extremely high clinical prevalence in both the community as well as in nosocomial patients. This behavior justifies the efforts that have been made to disseminate the present knowledge on urinary tract infections to the members of most clinical specialities. In the present review the authors discuss the new concept on the etiology, pathogenesis, diagnosis and treatment of urinary tract infections, with emphasis on the practical clinical approach to such cases.As infecções do trato urinário representam problema de grande relevância clínica, não só pela elevada freqüência com que acometem mulheres e homens vivendo na comunidade, mas também por representar a primeira causa de infecção em pacientes hospitalizados.Na presente revisão, o autor apresenta os conceitos atuais sobre a epidemiologia, os fatores etiopatogênicos, as manifestações clínicas e os métodos de diagnóstico das infecções do trato urinário. Finaliza discutindo as controvérsias e as novas diretrizes que envolvemo tratamento e a prevenção dessas infecções

Recurrent vesicourethal stenosis after radical prostatectomy: how to treat it?

Vesicourethral anastomotic stricture and urinary incontinence are severe complications of radical prostatectomy because they cause great impact in the quality of life. Three patients that presented these complications after prostate radical surgery were assessed retrospectively. To treat the stenosis of the vesicourethral anastomosis an urolume was placed and later on, an artificial sphincter AMS 800 was implanted to treat the resulting urinary incontinence.Universidade Federal de São Paulo (UNIFESP), Escola Paulista de Medicina (EPM) Department of UrologyUNIFESP, EPM, Department of UrologySciEL